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[ CAS No. 99-20-7 ] {[proInfo.proName]}

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Chemical Structure| 99-20-7
Chemical Structure| 99-20-7
Structure of 99-20-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 99-20-7 ]

CAS No. :99-20-7 MDL No. :MFCD00006628
Formula : C12H22O11 Boiling Point : -
Linear Structure Formula :- InChI Key :HDTRYLNUVZCQOY-LIZSDCNHSA-N
M.W : 342.30 Pubchem ID :7427
Synonyms :
D-Trehalose;α,α-Trehalose;NSC 2093;Trehalose;D-(+)-Trehalose

Calculated chemistry of [ 99-20-7 ]

Physicochemical Properties

Num. heavy atoms : 23
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 4
Num. H-bond acceptors : 11.0
Num. H-bond donors : 8.0
Molar Refractivity : 68.12
TPSA : 189.53 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -11.36 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.98
Log Po/w (XLOGP3) : -4.18
Log Po/w (WLOGP) : -5.4
Log Po/w (MLOGP) : -4.37
Log Po/w (SILICOS-IT) : -4.4
Consensus Log Po/w : -3.47

Druglikeness

Lipinski : 2.0
Ghose : None
Veber : 1.0
Egan : 1.0
Muegge : 4.0
Bioavailability Score : 0.17

Water Solubility

Log S (ESOL) : 0.94
Solubility : 2950.0 mg/ml ; 8.61 mol/l
Class : Highly soluble
Log S (Ali) : 0.81
Solubility : 2190.0 mg/ml ; 6.4 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : 4.25
Solubility : 6100000.0 mg/ml ; 17800.0 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 5.22

Safety of [ 99-20-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 99-20-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 99-20-7 ]

[ 99-20-7 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 25018-27-3 ]
YieldReaction ConditionsOperation in experiment
98% for 16h; Ambient temperature;
95% at 20℃; for 0.1h; sonication;
95% With iodine at 50℃; for 0.166667h; Microwave irradiation; 2.3. Typical procedure for per-O-acetylation of D-glucose General procedure: To a 10.0 mL round bottom flask, D-glucose (2.0 mmol) and acetic anhydride (12.0 mmol, 1.2 equiv. per OH) in the IL400 (2.0mL) was added I2 (0.05 mmol) at room temperature. Then themixture was heated to 50 °C under MW irradiation (200 W) until the TLC analysis showed that the reaction was complete.Then the reaction mixture was cooled to room temperature,and toluene (2.0 mL × 3) was added. The mixture was vigorously stirred for several minutes and then kept stationary. The upper toluene layer containing the product was collected. Toluene was removed by a rotary evaporator, and the crude product was purified by recrystallization in ethyl alcohol. The desired peracetylated sugars were obtained in 90%-99% yields. The bottom phase was the ionic liquid containing the I2 catalyst and produced acetic acid. The I2/IL400 system was reused after the removal of the acetic acid under reduced pressure.
With pyridine
With sulfuric acid
With H-Beta zeolite for 6h; Ambient temperature; Yield given;
With pyridine; dmap at 20℃; for 16h; 3 EXAMPLE 3 Compounds 7-15 can be prepared as follows: The appropriate anhydride (13.5 eq) is added to a solution of α,α-D-trehalose dihydrate (1 eq) in pyridine (1 mL). A catalytic amount of 4-dimethylaminopyridine (DMAP) (0.1 eq) is added, and the solution is stirred at room temperature for 16 hours. The solvent is removed by rotary evaporation, and the residue is purified by silica gel chromatography.

  • 2
  • [ 99-20-7 ]
  • [ 76-83-5 ]
  • 6-O-(triphenylmethyl)-α-D-glucopyranosyl-6'-O-(triphenylmethyl)-α-D-glucopyranoside [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With pyridine at 20 - 40℃; for 20h; Inert atmosphere;
88% In pyridine
83% With pyridine at 40℃; for 36h;
74% With pyridine at 20℃; for 17.5h;
With pyridine
With pyridine at 40℃;
With pyridine at 40℃; for 6h;
In pyridine at 20℃; for 96h;
With pyridine at 20 - 60℃; for 5h; 4-1 <4-l> Introduction of Trityl (Tr) Protecting GroupTrehalose hydrate (2.2 g, 5.82 mmol) and trityl chloride (7.7 g, 27.21 mmol) were dissolved in pyridine (40 mi) at room temperature and stirred for 5 hours while being slowly heated to 60 ºC .After the completion of the reaction, the reaction mixture was diluted with ethyl acetate and the extract was washed with aqueous hydrochloric acid (IN) and saturated aqueous NaHCO3. Thereafter, aqueous NaCl was added dropwise thereto to obtain a suspension. The suspension was filtered using a Buchner funnel. The filtrate thus obtained was washed with diethylether, and dried under a reduced pressure to obtain a white compound (4.37 g).m.p. 275-276 ºC (dec.)1H NMR (in MeOD, δ) 3.37 (app. t, 6H, J=3.8 Hz), 3.57 (dd, 2H, J=9.7 and 3.8 Hz), 3.79 (app. t, 2H, J=9.3 Hz), 4.02-4.09 (m, 2H), 5.36 (d, 2H, J=3.8 Hz, anomeric protons), 7.14-7.25 (m, 18H, trityl protons), 7.41-7.52 (m, 12H, trityl protons).
With pyridine
In pyridine at 20 - 60℃; for 5h; 4.4-1 Preparative Example 4Preparation of Trehalose Having the Same Two Protecting Groups<4-1> Introduction of Trityl (Tr) Protecting Group Trehalose hydrate (2.2 g, 5.82 mmol) and trityl chloride (7.7 g, 27.21 mmol) were dissolved in pyridine (40 ml) at room temperature and stirred for 5 hours while being slowly heated to 60° C.After the completion of the reaction, the reaction mixture was diluted with ethyl acetate and the extract was washed with aqueous hydrochloric acid (1N) and saturated aqueous NaHCO3. Thereafter, aqueous NaCl was added dropwise thereto to obtain a suspension. The suspension was filtered using a Buchner funnel. The filtrate thus obtained was washed with diethylether, and dried under a reduced pressure to obtain a white compound (4.37 g).m.p. 275-276° C. (dec.)1H NMR (in MeOD, δ) 3.37 (app. t, 6H, J=3.8 Hz), 3.57 (dd, 2H, J=9.7 and 3.8 Hz), 3.79 (app. t, 2H, J=9.3 Hz), 4.02-4.09 (m, 2H), 5.36 (d, 2H, J=3.8 Hz, anomeric protons), 7.14-7.25 (m, 18H, trityl protons), 7.41-7.52 (m, 12H, trityl protons).
With pyridine at 20 - 90℃; for 7h; Inert atmosphere; 4.2. Synthesis of 6-O-octyltrehalose (mono-C8) A solution of triphenylmethyl chloride (14.0 g; 50.0 mmol) in pyridine (25.0 mL) was added to a dispersion of trehalose dihydrate (3.78 g, 10.0 mmol) in pyridine (15.0 mL) at room temperature under argon and the mixture was stirred at 90 °C for 7 h. After the reaction mixture was cooled to room temperature, acetic anhydride (18.9 mL, 200 mmol) was added and the solution was stirred for 24 h at that temperature. After the mixture was coevaporated with toluene three times for concentration and diluted with chloroform, the solution was successively washed with water, dried over anhydrous Na2SO4, filtered, and evaporated. The residue was subjected to column chromatography using silica gel (eluent; hexane/ethyl acetate = 4:1 (v/v)) to give the 1' (6.96 g, 6.19 mmol) in 61.9% yield. 1H NMR (CDCl3) δ 1.75, 1.89, 1.99 (3s, 18H, CH3), 3.10 (d, 4H, H-6,6', J = 3.7 Hz), 4.08-4.13 (m, 2H, H-5,5'), 5.14, 5.19 (t, dd, 4H, H-2,2',4,4', J = 10.8 Hz, J = 10.8, 4.4 Hz), 5.45 (t, 2H, H-3,3', J = 9.8 Hz) 5.46 (d, 2H, H-1,1', J = 3.6 Hz), 7.15-7.41 (m, 30H, aromatics).Under argon, a mixture of 1' (6.96 g, 6.19 mmol) and sodium methoxide (0.065 g, 1.02 mmol) in a mixed solvent of methanol (35.0 mL) and THF (35.0 mL) was refluxed for 5 d. After the reaction mixture was cooled to room temperature, it was treated with cation-exchange resin (Amberlite IR-120 H+ form) for 30 min. The resin was filtered off and the filtrate was concentrated to give 1 (3.67 g, 6.45 mmol) quantitatively. 1H NMR (DMSO-d6 + D2O) δ 3.00-4.06 (m, 12H, H-2,2',3,3',4,4',5,5',6,6'), 5.15 (d, 2H, H-1,1', J = 3.2 Hz), 7.10-7.44 (m, 30H, aromatics).Under argon, to a dispersion of NaH (1.63 g, 27.1 mmol) in DMF (20.0 mL) was added a solution of 1 (1.50 g, 1.81 mmol) in DMF (12.0 mL) at room temperature and the mixture was stirred at that temperature for 30 min. After benzyl bromide (1.95 mL, 16.3 mmol) and tetrabutylammonium bromide (small amount) were added to the mixture, the reaction was conducted at room temperature for 6 d. After the resulting mixture was concentrated and diluted with ethyl acetate, the solution was washed with water, dried over anhydrous Na2SO4, filtered, and evaporated. The residue was recrystallized from methanol/1-propanol (1:0.54 (v/v)) to give 2 (2.51 g, 1.83 mmol) quantitatively. 1H NMR (CDCl3) δ 3.04 - 4.24 (m, 12H, H-2,2',3,3',4,4',5,5',6,6'), 4.64-4.95 (m, 12H, CH2-Ph), 5.46 (d, 2H, H-1,1', J = 3.6 Hz), 6.76-7.57 (m, 60H, aromatics).A mixture of 2 (2.37 g, 1.73 mmol) in a mixed solvent of acetic acid (5.0 mL) and 1,2-dichloroethane (5.0 mL) was refluxed for dissolution. Water (1.50 mL), 1,2-dichloroethane (5.0 mL), and concentrated hydrochloric acid (approximately 15 drops) were added, in this order, to the mixture at that temperature and the mixture was kept at that temperature for another 10 min. After the reaction mixture was cooled to room temperature and diluted with 1,2-dichloroethane, it was neutralized by the addition of saturated aqueous NaHCO3 with stirring, diluted with water, and extracted with chloroform. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated. The residue was subjected to column chromatography using silica gel (eluent; hexane/ethyl acetate = 5:1→3:1 (v/v)) to give 3 (0.99 g, 1.12 mmol) in 64.9% yield. 1H NMR (CDCl3) δ 3.49-3.59 (m, 8H, H-2,2',4,4',6,6'), 4.04 - 4.09 (m, 4H, H-3,3',5,5'), 4.63-5.01 (m, 12H, CH2-Ph), 5.12 (d, 2H, H-1,1', J = 3.6 Hz), 7.26-7.37 (m, 30H, aromatics).Under argon, to a dispersion of NaH (0.11 g, 1.70 mmol) in DMF (15.0 mL) was added a solution of 3 (0.51 g, 0.57 mmol) in DMF (5.0 mL) at room temperature and the mixture was stirred at that temperature for 30 min. Then, 1-bromooctane (0.33 mL, 1.70 mmol) and tetrabutylammonium bromide (small amount) were added to the mixture and the reaction was allowed to proceed at 80 °C for 24 h. After the reaction mixture was diluted with water and extracted with chloroform, the organic layer was dried over anhydrous Na2SO4, filtered, and evaporated. The residue was subjected to column chromatography on silica gel (eluent; hexane/ethyl acetate = 40:1→10:1→5:1 → 3:1 (v/v)) to give 4-C8 (0.18 g, 0.16 mmol) in 28.9% yield. 1H NMR (CDCl3) δ 0.85 (t, 3H, CH3, J = 6.8 Hz), 1.22-1.28 (m, 10H, -(CH2)5-CH3), 1.42-1.55 (m, 2H, -O-CH2-CH2-), 3.25-3.70 (m, 10H, H-2,2',4,4',6,6', -O-CH2-CH2-), 4.01-4.11 (m, 4H, H-3,3',5,5') 4.58-5.01 (m, 12H, CH2-Ph), 5.16, 5.18 (2d, 2H, H-1,1', J = 3.2, 4.0 Hz), 7.24-7.36 (m, 30H, aromatics).To a solution of 4-C8 (0.033 g, 0.030 mmol) in a mixed solvent of butanol (4.0 mL), methanol (0.40 mL), and water (0.13 mL) was added 10% palladium on carbon (0.0155 g) and the mixture was stirred at 60 °C for 3 d under hydrogen atmosphere. The reaction mixture was then filtered, and the filtrate was evaporated and dried under reduced pressure to give mono-C8 (0.015 g, 0.031 mmol) quantitatively. 1H NMR (CD3OD) δ 0.80 (t, 3H, CH3, J = 6.8 Hz), 1.14-1.32 (m, 10H, -(CH2)5-CH3), 1.44-1.49 (m, 2H, -O-CH2-CH2-), 3.35-3.85 (m, 14H, H-2,2',3,3',4,4',5,5',6,6', -O-CH2-CH2-), 4.996, 5.004 (2d, 2H, H-1,1', J = 2.8, 3.6 Hz); MALDI-TOF MS: Calcd [C20H38O11]Na+: m/z 477.2312. Found: m/z 477.4337.
Stage #1: TREHALOSE; trityl chloride With pyridine at 40℃; for 16h; Inert atmosphere; Stage #2: In methanol for 0.5h; Inert atmosphere; 2,2',3,3',4,4'-hexabenzyl-α,α-D-trehalose (2) This compound was prepared by a slight modification of Gilbertson’s procedures. To a clear solution of trehalose dihydrate (10.0 g, 26.43mmol) in dried pyridine (120ml) was added triphenylmethyl chloride (36.84 g, 132.16mmol). The mixture was stirred under N2 at 40 °C for 16 h. Dry MeOH (80 ml) was added and the reaction mixture was stirred for another 30min. Evaporation of solvent afforded yellowish solid, which was mixed with Et2O (200ml). Filtration and washing the solid with Et2O for several times until the disappearance of the tritylresidue checked by TLC followed by washing with 3% NaHCO3 solution anddrying in vacuum gave a white solid (25 g). The crude bistritylated trehalose was dissolved in DMF (200 ml) and added 80% NaH (15.86 g, 528.60mmol). After stirring under nitrogen at room temperature for 1 h, benzyl bromide (37.7ml, 317.2mmol) was added and the reaction mixture was stirred for 48 h. Distillation under vacuum removed most of the solvent and the residue was diluted with EtOAc. Ice water was then added. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After evaporation of solvent, the yellowish oil was dissolved in CH2Cl2 (100 ml) and MeOH (100 ml) and TsOH-H2O (15.1 g, 79.3mmol) was added. After stirring for 12 h, the reaction was quenched with 5 ml of Et3N. Evaporation of solvent and purification of the crude product by gradient flash silica gel chromatography (hexane/ethyl acetate: 4~1/1) afforded 2 as a viscous oil (8.20 g, 35%).
With pyridine at 40℃;
With pyridine
With pyridine at 75℃;
With pyridine

Reference: [1]Mishra, Vivek K.; Buter, Jeffrey; Blevins, Molly S.; Witte, Martin D.; Van Rhijn, Ildiko; Moody, D. Branch; Brodbelt, Jennifer S.; Minnaard, Adriaan J. [Organic Letters, 2019, vol. 21, # 13, p. 5126 - 5131]
[2]Brown, John M.; Cook, Stephen J.; Jones, Richard H.; Khan, Riaz [Tetrahedron, 1986, vol. 42, # 18, p. 5089 - 5096]
[3]Location in patent: experimental part Baddeley, Thomas C.; Wardell, James L. [Journal of Carbohydrate Chemistry, 2009, vol. 28, # 4, p. 198 - 221]
[4]Jacobsen, Kristian M.; Keiding, Ulrik B.; Clement, Lise L.; Schaffert, Eva S.; Rambaruth, Neela D. S.; Johannsen, Mogens; Drickamer, Kurt; Poulsen, Thomas B. [MedChemComm, 2015, vol. 6, # 4, p. 647 - 652]
[5]Bredereck [Chemische Berichte, 1930, vol. 63, p. 959,964]
[6]Penades, S.; Coteron, J. M. [Journal of the Chemical Society. Chemical communications, 1992, # 9, p. 683 - 684]
[7]Coterón, Jose M.; Vicent, Cristina; Bosso, Claude; Penadés, Soledad [Journal of the American Chemical Society, 1993, vol. 115, # 22, p. 10066 - 10076] Gilbertson, Scott R.; Chang, Cheng-Wei T. [Journal of Organic Chemistry, 1995, vol. 60, # 19, p. 6226 - 6228]
[8]Reynolds, Robert C.; Bansal, Namita; Rose, Jerry; Friedrich, Joyce; Suling, William J.; Maddry, Joseph A. [Carbohydrate Research, 1999, vol. 317, # 1-4, p. 164 - 179]
[9]Current Patent Assignee: POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY - WO2010/11012, 2010, A1 Location in patent: Page/Page column 24
[10]Location in patent: scheme or table Jiang, Yong-Li; Tang, Long-Qian; Miyanaga, Satoshi; Igarashi, Yasuhiro; Saiki, Ikuo; Liu, Zhao-Peng [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1089 - 1091]
[11]Current Patent Assignee: POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY - US2011/224423, 2011, A1 Location in patent: Page/Page column 11-12
[12]Location in patent: experimental part Kanemaru, Manami; Yamamoto, Kazuya; Kadokawa, Jun-Ichi [Carbohydrate Research, 2012, vol. 357, p. 32 - 40]
[13]Jiang, Yong-Li; Miyanaga, Satoshi; Han, Xiu-Zhen; Tang, Long-Qiang; Igarashi, Yasuhiro; Saiki, Ikuo; Liu, Zhao-Peng [Journal of Antibiotics, 2013, vol. 66, # 9, p. 531 - 537]
[14]Garifullin; Sharipova; Strobykina; Andreeva; Kravchenko; Kataev [Russian Journal of Organic Chemistry, 2015, vol. 51, # 10, p. 1488 - 1498][Zh. Org. Khim., 2015, vol. 51, # 10, p. 1517 - 1528,12]
[15]Garifullin; Sharipova; Strobykina, I. Yu.; Andreeva; Kataev [Chemistry of Natural Compounds, 2015, vol. 51, # 5, p. 886 - 889][Khim. Prir. Soedin., 2015, # 5, p. 760 - 763,4]
[16]Locatelli, Alessandra; Iommarini, Luisa; Graziadio, Alessandra; Leoni, Alberto; Porcelli, Anna Maria; Iotti, Stefano; Malucelli, Emil; Francia, Francesco; Venturoli, Giovanni; Farruggia, Giovanna [RSC Advances, 2019, vol. 9, # 27, p. 15350 - 15356]
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  • 3
  • [ 99-20-7 ]
  • [ 98-59-9 ]
  • [ 23235-67-8 ]
YieldReaction ConditionsOperation in experiment
With pyridine
With pyridine for 0.583333h;
With pyridine at 0 - 20℃; Inert atmosphere; 1.1.5 Synthesis of Hexa-O-acetyl-6,6’-di-0-toluene-p-sulphonyl-a,a-trehalose (Reagent R1): A solution of p-Toluenesulfonyl Chloride (37.8 g, 0.198 mol) in dry Pyridine (200 mL, 2.49 mol) was added drop-wise over 1 h to an ice-cooled solution of Trehalose Dihydrate (30 g, 79 mmol) in dry Pyridine (200 mL, 2.49 mol) under N2, and the reaction mixture was allowed to warm to room temperature. Further additions of /i-Toluenesulfonyl Chloride (7.56 g, 40 mmol) in dry Pyridine (10 mL, 0.125 mol) were made after 3.5 h, 24 h, 29 h, and 47 h. After an additional 3.5 h, the reaction mixture was cooled to 0 °C, Acetic anhydride (400 mL, 4.23 mol) was added drop-wise, and allowed to warm to room temperature. After 24 h, the reaction mixture was poured into ice-water (2 L) and stirred overnight. The mixture was filtered, and white solids were collected. Recrystallisation (2x) from MeOH (300 mL + 440 mL) gave Reagent Rl (12.3 g, 95% pure, 16%) as white needles: NMR (500 MHz, CDCh) d 7.74 (d, J= 8.3 Hz, 4H, Ar), 7.35 (d, J= 8.0 Hz, 4H, Ar), 5.40 (dd, J2= 9.9 Hz, J3A= 9.2 Hz, 2H, H-3, H-3’), 4.95 (dd, J3= 9.9 Hz, Ju= 3.8 Hz, 2H, H-2, H2’), 4.92 (d, J = 4.1 Hz, 2H, H-l, H-L), 4.91 (dd, J4,s =10.1 Hz, J3,4= 9.2 Hz, 2H, H-4, H-4’), 4.10 (ddd, J4,5= 10.1 Hz, j5,6b= 5.6 Hz, J5,6a= 2.8 Hz, 2H, H- 5, H-5’), 4.08 - 4.02 (m, 4H, H-6a, H-6a H-6b, H6b’), 2.45 (s, 6H, 2x C6H4CH3), 2.08 (s, 6H, 2x OCOCH3), 2.02 (s, 6H, 2x OCOCH3), 2.00 (s, 6H, 2x OCOCH3) ppm.13C NMR (126 MHz, CDCh) d 170.07 (2C, 2x OCOCH3) 169.71 (2C, 2x OCOCH3), 169.69 (2C, 2x OCOCH3),145.45 (2C, 2x Ar), 132.56 (2C, 2x Ar), 130.02 (4C, 4x Ar), 128.20 (4C, 4x Ar), 92.95 (2C, C-l, C-L), 69.95 (2C, C-3, C-3’), 69.36 (2C, C-2, C-2’), 68.73 (2C, C-4, C-4’), 68.32 (2C, C-5, C- 5’), 67.70 (2C, C-6, C-6’), 21.82 (2C, 2x C6H4CH3), 20.78 (2C, 2x OCOCH3), 20.73 (2C, 2x OCOCH3), 20.71 (2C, 2x OCOCH3) ppm.
  • 4
  • [ 99-20-7 ]
  • [ 10416-59-8 ]
  • [ 59578-12-0 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: TREHALOSE; N,O-bis-(trimethylsilyl)-acetamide With tetrabutyl ammonium fluoride Stage #2: With potassium carbonate
50% With tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at 20℃; for 2h; 7 2,2',3,3,,4,4,-Hexa-0-trimethylsilyl- α,α'-D-trehalose: α,α'-D-trehalose (5 g, 0.013 mol) was co-evaporated with DMF (2 x 25 mL) and d issolved in DMF (30 mL). To this solution was added BSA (22.4 mL, 0.13 mmol) and TBAF (1.25 mL, 1.3 mmol) and the resulting solution was stirred at room temperature for two hours. The reaction was quenched with isopropa nol (2 mL) and diluted with MeOH (100 mL). K2CO3 (0.359 g) was added and the reaction was left to stir for a further 2 hours. The reaction mixture was concentrated in vacuo, partitioned between ether and brine, dried over MgSCU, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography to give the title compound as white crystals (5.02 g, 6.47 mmol, 50%).
With tetrabutyl ammonium fluoride; potassium carbonate 1) DMF, THF, r.t., 30 min, 2) MeOH, 0 deg C, 2 h; Yield given. Multistep reaction;
Stage #1: TREHALOSE; N,O-bis-(trimethylsilyl)-acetamide With tetrabutyl ammonium fluoride In 1-methyl-pyrrolidin-2-one Stage #2: With potassium carbonate In 1-methyl-pyrrolidin-2-one; methanol

  • 5
  • [ 99-20-7 ]
  • [ 10416-59-8 ]
  • [ 42390-78-3 ]
YieldReaction ConditionsOperation in experiment
98% With tetrabutyl ammonium fluoride In tetrahydrofuran Ambient temperature;
With tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at 15 - 20℃; for 0.75h;
With tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at 0℃; for 2h; Inert atmosphere;
  • 6
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • [ 18929-82-3 ]
YieldReaction ConditionsOperation in experiment
94% With toluene-4-sulfonic acid In N,N-dimethyl-formamide for 0.75h;
91% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 2h;
87% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 1h; 2 [000165] 4, 6-0-benzylidene-a-D-glucopyranosyl-(l→l)-4 ', 6 '-O-benzylidene-a-D- glucopyranoside (10). 000165] 4, 6-0-benzylidene-a-D-glucopyranosyl-(l→l)-4 ', 6 '-O-benzylidene-a-D- glucopyranoside (10). To a flame dried round bottom flask was added anhydrous trehalose (5 g, 14.6 mmol, 1 eq), j-toluene sulphonic acid monohydrate (0.11 g, 0.6 mmol, 0.04 eq), and DMF (75 mL). Dimethoxy toluene (4.7 mL, 32.1 mmol, 2.2 eq) was added in two equal portions 20 minutes apart while maintaining the reaction temperature at 100°C. The mixture was stirred at 100°C for an additional 40 minutes before removal of excess DMF in vacuo to produce a viscous liquid. The liquid was further purified first by recrstalization from xylenes followed by recrystalization from a mixture of ethanohwater (1 :3) to yield long white needles as the final roduct (6.6 g, 13 mmol, 87% yield).
86% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 65℃; for 2h; reflux;
84% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 60℃;
With toluene-4-sulfonic acid In N,N-dimethyl-formamide

  • 7
  • [ 99-20-7 ]
  • [ 999-97-3 ]
  • [ 42390-78-3 ]
YieldReaction ConditionsOperation in experiment
96% With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 20℃; for 0.25h; Inert atmosphere;
94% With pyridine; chloro-trimethyl-silane at 0 - 20℃;
With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 20℃; Inert atmosphere; regioselective reaction;
  • 8
  • [ 99-20-7 ]
  • [ 52290-50-3 ]
YieldReaction ConditionsOperation in experiment
75% With iodine; triphenylphosphine In N,N-dimethyl-formamide at 80℃; for 2h; 7 6,6'-Dideoxy-6,6'-diiodo-ci,c -trehalose α, a -Trehalose dihydrate (2.01 g, 5.31 mmol) was co-evaporated with DMF (40 mL), then d issolved in DMF (60 mL) and the volume reduced by one third. Triphenylphosphine (6.99 g, 26.6 mmol) and I2 (5.41 Q> 21 -3 mmol) were added and the resulting solution was stirred at 80°C for 2 hours. The mixture was concentrated to one third of the volume, diluted with MeOH (80 mL), and the pH was adj usted to 8 with NaOMe. After stirring for 30 min, the mixture was neutralised with Dowex-H+, filtered, and the resin washed with MeOH. The MeOH was removed in vacuo and the resultant sludge poured into vigorously stirred water (80 mL). The solid was removed by filtration over celite a nd the filtrate extracted with CH2CI2 (3 x 130 mL). The aqueous layer was concentrated to give a yellow residue which was further purified by HP20 chromatography (H2O to H20: MeOH, 1 : 1, v/v) to give the title compound as a white solid (2.25 g, 4.00 mmol, 75%).
75% With iodine; triphenylphosphine In N,N-dimethyl-formamide at 20 - 80℃; for 2h; Inert atmosphere;
With iodine; sodium methylate; triphenylphosphine 1.) DMF, 80 deg C, 1.5 h, 2.) DMF, methanol, RT, 30 min; Yield given. Multistep reaction;
With iodine; sodium methylate; triphenylphosphine 1.) DMF, 90 deg C, 3.5 h; 2.) MeOH, 0 deg C, 1 h; Yield given; Multistep reaction;
With N-iodo-succinimide; triphenylphosphine In N,N-dimethyl-formamide
Stage #1: TREHALOSE With iodine; triphenylphosphine In N,N-dimethyl-formamide at 80℃; for 4h; Stage #2: With sodium methylate In methanol; N,N-dimethyl-formamide at 20℃; for 0.5h; 2,2’,3,3’,4,4’-Hexa-O-acetyl-6,6’-dideoxy-6,6-diiodo-α,α-D-trehalose (4). Iodine (9.95 g, 39.2 mmol) was added to a solution of triphenylphosphine (10.28 g, 39.2 mmol) in DMF (40 mL) at 0 °C, and all substances were completely dissolved. To the solution was added dried trehalose 2 (3.0 g, 9.80 mmol) at rt, and the mixture was stirred at 80 °C for 4 h. The mixture was concentrated to half of its volume, and 3 M methanolic NaOMe (ca. 16 mL) was added to the mixture. At this time, the mixture showed ca. pH 9 on pH paper, and the mixture was stirred for 30 min at an ambient temperature. TLC indicated complete conversion of intermediates to diodotrahalose 3 {Rf 0.17 [3:1 CHCl3-MeOH (v/v)], and water (100 mL) was added to the mixture to give an insoluble mass (most of Ph3P=O), which was filtered. The filtrate was concentrated in vacuo, and the residue was completely dried. The dried residue was allowed to react with Ac2O (40 mL) in pyridine (40 mL) at rt overnight. The reaction mixture was concentrated to 1/3 of its volume, and the mixture was poured into ice-cold water (400 mL) to give precipitates. The precipitates were filtered and dried in vacuo. The precipitates were recrystallized from EtOH (ca. 250 mL) to give the corresponding diiodo-acetate 4 (6.65 g) in 83.3% yield.

  • 9
  • [ 99-20-7 ]
  • octa-O-sulfonato-α,α-trehalose octasodium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With trimethyl-sulfo-ammonium betaine In N,N-dimethyl-formamide at 70℃; for 17h;
Stage #1: TREHALOSE With methyl chlorosulfate In N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere; Stage #2:
  • 10
  • [ 143-07-7 ]
  • [ 99-20-7 ]
  • trehalose monododecanoate [ No CAS ]
  • 6,6’-O-didodecanoyl-α,α’-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
In diethyl ether; water for 13h; Irradiation; Candida antarctica lipase (Novozym 435);
Stage #1: TREHALOSE With novozyme 435 In water at 80℃; Green chemistry; Enzymatic reaction; Stage #2: lauric acid In diethyl ether at 110℃; for 96h; Green chemistry; 2.2. General synthesis of sugar esters General procedure: Enzymatic synthesis of sugar esters under solvent-free conditionswas carried out using a modified method from Gelo-Pujic et al. [23].The sugar substrate (1 mmol) was dissolved in 2 mL of water in a 50 mLround bottle and then impregnated on Novozyme 435 (0.034, 0.17,0.34 and 0.68 g/mol of sugar substrate) by evaporating the aqueoussolution under a reduced pressure by heating in a water bath. Here, awater bath temperature of up to 80 °C was used.The lipid substrate (La or LaEt) (1, 2, 3 or 4 mmol) dissolved indiethyl ether (Et2O) was added to the dried mixture. Here, adding LaEtwithout Et2O was also tried for a comparative study. The Et2O in thereaction mixture was evaporated completely prior to starting the reaction.The content in the oil bath was heated at different temperatures(50, 60, 70, 80, 90, 100, 110, 120, 130 and 150 °C) and monitored forvarious reaction times (6, 12, 24, 48, 72 and 96 h). After the reactionmixtures were cooled down to ambient temperatures, they were extracted by N,N-dimethylformamide (DMF) at 60 °C under ultrasonicationtreatment. Some sugar esters such as trehalose monoester(TME), trehalose diester (TDE) and glucose monoester (GME) wereisolated via silica gel column chromatography using a mixed solventsystem [chloroform/methanol/acetone/water=9/4/4/1 (v/v/v/v)] asan eluent. The nuclear magnetic resonance (NMR) spectra of TME, TDEand GME were consistent with the reported data for 6-O-lauroyl trehalose,6,6′-O-dilauroyl trehalose and 6-O-lauroyl-α-D-glucopyranose[30-32] (Figure S1, Supplementary Material), and the obtained sampleswere of high purity.
  • 11
  • [ 99-20-7 ]
  • [ 18933-88-5 ]
YieldReaction ConditionsOperation in experiment
89% With hydrogen azide; di-isopropyl azodicarboxylate; triphenylphosphine In N,N-dimethyl-formamide; toluene at 0 - 20℃; for 25h; Inert atmosphere; regioselective reaction;
11% Stage #1: TREHALOSE With di-isopropyl azodicarboxylate; triphenylphosphine In 1,4-dioxane at 20℃; for 0.5h; Stage #2: With hydrogen azide In 1,4-dioxane; toluene for 66h;
With methanol; sodium azide; carbon tetrabromide; triphenylphosphine 1.) DMF, room temperature, 24 h, 2.) 120 deg C, overnight; Multistep reaction;
Multi-step reaction with 5 steps 1: 98 percent / ZnCl2 / 144 h / 20 °C 2: 80 percent / pyridine / 64 h / 20 °C 3: 80 percent / NBS; K2CO3 / CCl4 / 2 h / Heating 4: 90 percent / NaN3 / dimethylformamide / 14 h / 65 °C 5: 73 percent / NaOMe / methanol / 48 h / 20 °C
With sodium azide; triphenylphosphine In tetrachloromethane
With hydrogen azide; di-isopropyl azodicarboxylate; triphenylphosphine In N,N-dimethyl-formamide; toluene at 0 - 20℃;

  • 12
  • [ 99-20-7 ]
  • [ 922-69-0 ]
  • C18H30O13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 0℃; for 4h;
  • 13
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • 4,6;4',6'-di-O-benzylidene-α,α-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
91% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 2h;
91% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60 - 100℃;
90% With toluene-4-sulfonic acid Inert atmosphere;
90% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;
84% In N,N-dimethyl-formamide at 60℃; for 1h; 1.A 1. Benzylidenation of α,α-trehalose α,α-Trehalose dihydrate (1 eq.) was dehydrated by boiling in absolute ethanol (0.4 M) under reflux for 30 min. The dry residue 1_ was then suspended in dry λ/,λ/-dimethylformamide (DMF, 0.4 M), and α,α-dimethoxytoluene (DMT, 2 eq.) was added, together with 10-camphorsulfonic acid (CSA, 0.05 eq.). The mixture was heated (60°C) during 1 h on a rotary evaporator with a light vacuum to eliminate the methanol. More DMT (0.25 eq.) and CSA (0.01 eq.) were then added and the mixture was attached again on the rotary evaporator. At the end of the reaction, DMF was evaporated. The mixture was stirred overnight in an aqueous sodium hydrogencarbonate solution (5 %) to give crystalline diacetal 2. The product was recrystallized by dissolution in boiling ethanol, addition of hot water, and slow cooling. Finally, the white crystals of 2 were filtered, washed with water and ether petroleum and dried (84 %).
83% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 0.216667h; sonication;
With hydrogen cation In N,N-dimethyl-formamide at 80℃; for 4h;
Stage #1: TREHALOSE With toluene-4-sulfonic acid In ethanol; toluene at 60℃; for 4h; Stage #2: benzaldehyde dimethyl acetal In N,N-dimethyl-formamide at 100℃; for 0.666667h;
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 1.16667h; 1.1-1; 2.2-1 Synthesis of 4,6,4′,6′-dibenzylidenated trehalose (4,6,4′,6′-dibenzylidenated trehalose) (Compound A) (step a in FIG. 1) Compound A was replaced by J. Carbohydr. Chem. It was prepared in 88% yield by modifying the process disclosed in 2009, 28, 198-221. p-Toluenesulfonic acid monohydrate (0.12 g, 0.7 mmol) was dehydrated via rotary evaporation of the suspension in toluene (30 mL). Commercially available α, α-trehalose dihydrate (5.00 g, 13.25 mmol) was dried at reflux for 4 hours in ethanol (30 mL) and dried overnight at 60° C. in high vacuum to remove crystalline water molecules. Of p-toluenesulfonic acid (catalyst amount) and (dimethoxymethyl)benzene (2 mL, 13.25 mmol) mixed in dry DMF (20 mL) to a suspension of residual anhydrous trehalose in dried DMF (20 mL) The solution was added. The mixture was heated at 100 °C for 30 minutes and concentrated at 50 °C. Further (dimethoxymethyl)benzene (2 mL, 13.25 mmol) was added and the heating procedure was repeated. An additional amount of (dimethoxymethyl)benzene (0.5 mL, 3.3 mmol) was added, and the mixture was heated in a steam bath for 10 minutes to obtain a colorless solution. The reaction was stopped by dropwise addition of Et3N (pH>7). The solvent was evaporated on a rotary evaporator, and a thick glassy liquid was purified by column chromatography to obtain 4, 6, 4', 6'-dibenzylideneated trehalose (Compound A) as a white solid.

Reference: [1]Sarpe, Vikram A.; Kulkarni, Suvarn S. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 38, p. 6460 - 6465]
[2]Yonehara, Koji; Hashizume, Tomohiro; Ohe, Kouichi; Uemura, Sakae [Bulletin of the Chemical Society of Japan, 1998, vol. 71, # 8, p. 1967 - 1972]
[3]Location in patent: experimental part Baddeley, Thomas C.; Wardell, James L. [Journal of Carbohydrate Chemistry, 2009, vol. 28, # 4, p. 198 - 221]
[4]Location in patent: scheme or table Tao, Houchao; Fu, Yu; Thompson, Aaron; Lee, Sung Chang; Mahoney, Nicholas; Stevens, Raymond C.; Zhang, Qinghai [Langmuir, 2012, vol. 28, # 30, p. 11173 - 11181]
[5]Dhaene, Shari; Van der Eycken, Johan; Beerens, Koen; Franceus, Jorick; Desmet, Tom; Caroen, Jurgen [Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, vol. 35, # 1, p. 1964 - 1989]
[6]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - WO2008/90425, 2008, A1 Location in patent: Page/Page column 19; 22-23
[7]Deng, Shenglou; Gangadharmath, Umesh; Chang, Cheng-Wei Tom [Journal of Organic Chemistry, 2006, vol. 71, # 14, p. 5179 - 5185]
[8]Shin, Seunghoon; RajanBabu [Organic Letters, 1999, vol. 1, # 8, p. 1229 - 1232]
[9]Das, Manabendra; Du, Yang; Mortensen, Jonas S.; Ramos, Manuel; Ghani, Lubna; Lee, Ho Jin; Bae, Hyoung Eun; Byrne, Bernadette; Guan, Lan; Loland, Claus J.; Kobilka, Brian K.; Chae, Pil Seok [Organic and Biomolecular Chemistry, 2019, vol. 17, # 12, p. 3249 - 3257]
[10]Current Patent Assignee: HANYANG UNIVERSITY - KR2020/68883, 2020, A Location in patent: Paragraph 0147-0150; 0160-0162; 0172-0174; 0185; 0232; 0235
  • 14
  • [ 75-77-4 ]
  • [ 99-20-7 ]
  • [ 42390-78-3 ]
YieldReaction ConditionsOperation in experiment
96% With pyridine at 0 - 20℃; Inert atmosphere;
92% With pyridine at 20℃;
87% With pyridine at 0 - 20℃; for 16.5h; 2; 6 Per-O-(trimethylsilylVα.α-trehalose 5 The procedure was adapted from literature (Sizovs et al., 2013). Trehalose (2.0 g, 5.8 mmol) was dissolved in pyridine (50 mL) and let stir 20 minutes until homogeneous. The reaction was cooled to 0 °C and chlorotrimethyl silane (7.11 mL, 56.1 mmol) was added dropwise. The reaction was stirred an additional 30 minutes at 0 °C and warmed to room temperature. After 16 hours, the reaction was cooled again to 0 °C and poured into cold pH 9 carbonate buffer (50 mM, 150 mL). Aqueous workup was performed by extracting with 3 x 70 mL hexanes. The organic layers were combined and washed with brine (50 mL) then dried over MgS04. The solvent was removed and the product was freeze-dried from benzene to obtain solid/oil (4.7 g, 5.11 mmol, 87% yield). 1H-NMR (400 MHz, CDC13) δ: 4.91 (d, J = 3.2 Hz, 2H), 3.89 (t, J= 8.0 Hz, 2H), 3.79 (dt, J = 1.4, 9.6 Hz, 2H), 3.68-3.67 (m, 4H), 3.43 (t, J= 9.0 Hz, 2H), 3.39 (dd, J = 3.2, 9.6 Hz, 2H), 0.14-0.10 (m, 72H). 13C-NMR (400 MHz, CDC13) δ = 94.4, 73.6, 73.2, 72.9, 71.8, 62.2, 1.2, 0.9, 0.2, -0.3. ESI-MS (MeCN): calculated for C36H86NaO11Si8 [M+Na]+: 941.42, observed: 941.26. Figure 17 shows 1H-NMR spectrum (CDC13) of per-O-(trimethylsilyl)-a,a-trehalose 5. Figure 18 shows 13C-NMR spectrum (CDC13) of per-O-(trimethylsilyl)-a,a-trehalose 5.
With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane
3.04 g With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere;
With pyridine at 20℃; for 26h; Inert atmosphere; Reflux; Preparation of 2,2',3,3',4,4'-hexa(trimethylsilyl)-α,α-D-trehalose (5) Compound 5 was prepared following Gensler's procedures. To a solution of trehalose dihydrate (10.0 g, 26.43mmol) in dry pyridine (100ml) was added trimethylsilyl chloride (50ml, 396mmol) at room temperature dropwise. After stirring at room temperature for 1 day, the mixture was refluxed for 2 h. Solvent was removed by distillation at reduced pressures. The residue, treated with 200ml of dry petroleum ether, was filtered. The crude persilylated trehalose was dissolved in dry pyridine (100ml). Water (10ml) and glacial acetic acid (3.3 ml) was then added at 8 °C. The cold solution was stirred under N2 for 14 h. The reaction mixture was poured over crushed ice and water (200 ml), and the two-phase system was extracted with several portions of petroleum ether. After the combined extract was washed several times with cold water, the organic layer was dried and concentrated. Purification of the crude product by gradient flash silica gel chromatography (hexane/ethyl acetate: 20~10/1) afforded 5 as a white solid (15 g, 73%). m.p. 115-117 °C. 1H NMR (600MHz, CDCl3) d 4.90 (d, J3.0Hz, 1H), 3.84-3.91 (m, 2H), 3.66-3.74 (m, 2H), 3.48 (t, J9.0Hz, 1H), 3.42 (dd, J3.0, 6.0Hz, 1H), 1.80 (t, J6.0Hz, 1H), 0.10-0.17 (m, 27H).
With triethylamine In dichloromethane at 0℃; for 24h;
With triethylamine
With pyridine at 0 - 20℃;
1.1 g With pyridine at 0 - 20℃; for 16h; 2,3,4,2',3',4’-Hexa-O-trimetylsilyl-α,α'-trehalose 37 Trehalose 1 (471.4 mg, 1.246 mmol, 1eq) was dissolved in pyridine (12 mL) and stirred for 20 minutes at RT, until complete dissolution. The reaction was cooled to 0°C and chlorotrimethyl silane (1.6 mL, 12.46 mmol, 10 eq) was added dropwise. The reaction was stirred for additional 30 minutes at 0°C and warmed to RT. After 16 hours the solvent was concentrated at reduced pressure. The white solid residue was dissolved in water (35 mL) and extracted with n-hexane (4 x 30 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuum to yield crude 36 (1.1 g) as a white solid that was used without purification in the next reaction step.Crude 36 (1.1 g, theoretically 1.24 mmoles) was dissolved in 3:1 MeOH/DCM (8 mL), cooled at 0°C under stirring, and solid K2CO3 (20.7 mg, 0.15 mmol, 0.12 eq) was added. The reaction was stirred for 15 minutes at 0°C, then at RT for 1 hour (TLC monitoring, eluant mixture: n-hexane/EtOAc 8:2). After reaction completion the reaction was quenched by addition of acetic acid (0.025 mL). The solvent was removed at reduced pressure, and the crude was purified by flash chromatography (eluant mixture: EtOAc/ n-hexane from 2:8 to 4:6), yielding 724.6 mg of pure 37 as a white solid (0.935 mmol, 75% yield over two steps).

Reference: [1]Lemetais, Aurelie; Bourdreux, Yann; Lesot, Philippe; Farjon, Jonathan; Beau, Jean-Marie [Journal of Organic Chemistry, 2013, vol. 78, # 15, p. 7648 - 7657]
[2]Bourdreux, Yann; Lemetais, Aurelie; Urban, Dominique; Beau, Jean-Marie [Chemical Communications, 2011, vol. 47, # 7, p. 2146 - 2148]
[3]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2016/25668, 2016, A1 Location in patent: Paragraph 00220-00221
[4]Davoust; Granet; Krausz; Carre; Guilloton [Tetrahedron Letters, 1999, vol. 40, # 13, p. 2513 - 2516]
[5]Location in patent: experimental part Sarpe, Vikram A.; Kulkarni, Suvarn S. [Journal of Organic Chemistry, 2011, vol. 76, # 16, p. 6866 - 6870]
[6]Jiang, Yong-Li; Miyanaga, Satoshi; Han, Xiu-Zhen; Tang, Long-Qiang; Igarashi, Yasuhiro; Saiki, Ikuo; Liu, Zhao-Peng [Journal of Antibiotics, 2013, vol. 66, # 9, p. 531 - 537]
[7]Kobayashi, Kurumi; Saito, Rumiko; Udagawa, Kaori; Miyano-Kurosaki, Naoko; Asano, Naoto; Iwanaga, Tetsuo; Teramoto, Naozumi; Shimasaki, Toshiaki; Shibata, Mitsuhiro [European Journal of Organic Chemistry, 2018, vol. 2018, # 26, p. 3444 - 3453]
[8]Fiolek, Taylor J.; Banahene, Nicholas; Kavunja, Herbert W.; Holmes, Nathan J.; Rylski, Adrian K.; Pohane, Amol Arunrao; Siegrist, M. Sloan; Swarts, Benjamin M. [ChemBioChem, 2019, vol. 20, # 10, p. 1282 - 1291]
[9]Colombo, Eleonora; Biocotino, Michele; Frapporti, Giulia; Randazzo, Pietro; Christodoulou, Michael S.; Piccoli, Giovanni; Polito, Laura; Seneci, Pierfausto; Passarella, Daniele [Pharmaceutics, 2019, vol. 11, # 8]
[10]Arosio, Daniela; Assoni, Giulia; Colombo, Eleonora; Frapporti, Giulia; Gornati, Davide; Perez-Carrion, Maria Dolores; Piccoli, Giovanni; Polito, Laura; Seneci, Pierfausto [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 40]
  • 15
  • [ 99-20-7 ]
  • [ 106-95-6 ]
  • [ 297740-82-0 ]
YieldReaction ConditionsOperation in experiment
70% With sodium hydride In N,N-dimethyl-formamide at 20℃;
70% With sodium hydride In N,N-dimethyl-formamide
  • 16
  • [ 615564-31-3 ]
  • [ 99-20-7 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogen In methanol for 24h;
  • 17
  • [ 99-20-7 ]
  • 6-bromo-6-deoxy-α,α'-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With N-Bromosuccinimide; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 48h;
33% With N-Bromosuccinimide; triphenylphosphine In N,N-dimethyl-formamide at 20 - 60℃; 6-deoxy-6-bromo-a-D-glucopyranosyl-a-D-glucopyranoside (19); The compound was synthesized according to the literature . In a 50 mL flask, anhydrous d-trehalose (1.52 g, 4.43 mmol, 1 eq) was dissolved in dry DMF (15mL). Triphenylphosphine (2.32 g, 8.87 mmol, 2 eq) was added followed by NBS (1.57 g, 8.87 mmol, 2 eq). The mixture was stirred overnight at room temperature and 24 h at +60 °C and evaporated to give 5.00g of a yellow oil containing a mixture of expected compound along with unreacted trehalose and corresponding dibromo. This oil was purified by column chromatography using (EtOAc: MeOH 100:0, 90: 10 and 80:20) to give (408.3 mg, 20%) and the titled compound as a brownish, amorphous solid (594.0 mg, 33%).+ 134 (c = 1 in (H20) [Lit. [αβ1 + 180.8 (C = 0.7 in CH3OH)]34; 1HNMR (400 MHz DEUTERIUM OXIDE) δ ppm : 3.33 (1 H, app t, J4 5- = J4 3-= 9.8 Hz, H-4'), 3.38 (1 H, app t, J4,5 = J4,3= 9.8 Hz, H-4), 3.53 (1 H, dd, J2,3 = 9.8 Hz, J2 = 3.8 Hz, H-2 ), 3.56 (1 H, dd, Jr,y = 9.8 Hz, Jr, = 3.8 Hz, H-2' ), 3.56 (1 H, dd, l6b,6a = 1 1.4 Hz, J6biS = 5A Hz, H-6b CH2Br ), 3.64 (1 H, dd, = 1 1.6 Hz, J6b;y = 5.0 Hz, H-6b' CH2OH ), 3.68 (1 H, dd, J6a,6b = 1 1.4 Hz, J6a,5 = 2.8 Hz, H-6a CH2Br ), 3.70 (1H, app t , 2 > = Jy,4 = 9.8 Hz, H-3 '), 3.73 (1 H, dd, ha ;6V = 1 1.4 Hz, J 2.6 Hz, H-6a' CH2OH ), 3.73 (1H, m, H-5 '), 3.75 (1H, app t , h,2 = Js,4 = 9.8 Hz, H-3), 3.87 (1 H, ddd, J5A = 9.8 Hz, JSi6b = 5.4 Hz, J5 = 2.8 Hz, H-5), 5.08 (1 H, d, J ,r = 3.8 Hz, H-l '), 5.10 (1 H, d, Ju = 3.8 Hz, H-l); 13C NMR (126 MHz DEUTERIUM OXIDE) δ ppm 34.1 (C-6 CH2Br), 60.8 (C-6' CH2OH), 69.9 (C-4'), 71.0 (C-4), 71.2, 71.2 (C-2 and C-2'), 71.9 (C-5), 72.4 (C-3), 72.5 (C-5 '), 72.8 (C-3 '), 93.6 (C-1), 93.8 (C-1 '); IR (KBr): v = 3421 , 2925, 1653, 1636, 1419, 1261 , 1 149, 1 103, 992, 939 cm"1 ; MS (ESI-) m/z 403.0 and 405.0 (M-H)~; HRMS (ESI ) calcd. for Ci2H20Oio79Br" (M- H)~: 403.0245, Found: 403.0241 , calcd. for Ci2H20Oio81Br" (M-H)~: 405.0227, Found: 405.0219.
With N-Bromosuccinimide; triphenylphosphine In N,N-dimethyl-formamide at 0 - 20℃;
  • 18
  • [ 99-20-7 ]
  • [ 75-03-6 ]
  • perethylated α,α-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
78.5% With sodium hydroxide In dimethyl sulfoxide at 20℃; for 120h;
  • 19
  • [ 99-20-7 ]
  • [ 107-08-4 ]
  • perpropylated α,α-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
65.21% With sodium hydroxide In dimethyl sulfoxide at 20℃; for 144h;
  • 20
  • [ 99-20-7 ]
  • [ 74-88-4 ]
  • [ 25018-29-5 ]
YieldReaction ConditionsOperation in experiment
92.4% With sodium hydroxide In dimethyl sulfoxide at 20℃; for 24h;
With sodium hydroxide In dimethyl sulfoxide for 2h; Sonication; 2.4. GC/MS analysis General procedure: The samples were permethylated before their analysis in GC-MS,according to the method of Ciucanu and Kerek [14]. Briefly, the driedsamples were taken up in a DMSO/NaOH/ICH3 mixture and incubatedfor 2 h in an ultrasonic bath. The reaction was stopped by adding waterand the permethylated compounds were extracted with CHCl3 andwashed seven times with water. The permethylated samples were finallydissolved in acetonitrile.
  • 21
  • 4,6;4',6'-di-O-benzylidene-α,α-D-trehalose [ No CAS ]
  • [ 99-20-7 ]
YieldReaction ConditionsOperation in experiment
98% With methanol; toluene-4-sulfonic acid at 20℃; for 0.0333333h; sonication;
  • 22
  • [ 108-05-4 ]
  • [ 99-20-7 ]
  • [ 68643-14-1 ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
With recombinant Cellvibrio japonicus acetyl esterase B aq. buffer; Enzymatic reaction; regioselective reaction;
  • 23
  • [ 99-20-7 ]
  • [ 123-20-6 ]
  • 6,6'-di-O-butanoyl-α,α'-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
  • 24
  • [ 99-20-7 ]
  • [ 4704-31-8 ]
  • Decanoic acid (2R,3S,4S,5R,6R)-6-((2R,3R,4S,5S,6R)-6-decanoyloxymethyl-3,4,5-trihydroxy-tetrahydro-pyran-2-yloxy)-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
  • 25
  • [ 99-20-7 ]
  • [ 5809-91-6 ]
  • 6,6'-di-O-myristoyltrehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
  • 26
  • [ 99-20-7 ]
  • [ 111-63-7 ]
  • [ 81105-75-1 ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
  • 27
  • [ 99-20-7 ]
  • [ 2177-18-6 ]
  • trehalose diacrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With novozyme 435 In acetone at 45℃; for 48h;
With lipase B from Candida antarctica In acetone at 50℃; for 48h; Enzymatic reaction; 1 Synthesis of Trehalose Diacrylate Enzymatic, chemoselective modification of trehalose to form trehalose diacrylate has been reported. See, John et al., 2006 and Zhu and Dordick, 2006, cited below, which are incorporated herein by reference as if fully set forth. An exemplary functional monomer was synthesized by reacting a four-mole excess of vinyl acrylate (CAS: 2 177-18-6) with trehalose dihydrate in the presence of Novozyme 435 (Lipase from Candida antarctica that is attached to acrylic resin) in dry acetone at 50°C. and agitated conditions (either by orbital shaker or magnetic stir plate) for 48 hours. Hydroquinone monomethyl ether (MEHQ) and butylated hydroxytoluene (BHT) were used to prevent excessive radical homopolymerizaiton of the product. The crude product was purified via silica flash chromatography on an ISCO Combiflash system using ethyl acetate and 80% methanol as the binary solvent system. Product was characterized using LC-MS (FIG. 2) and ‘H-NMR (FIG. 3). See Reaction Scheme 3, below.
  • 28
  • [ 99-20-7 ]
  • [ 50-99-7 ]
YieldReaction ConditionsOperation in experiment
With McIlvaine buffer at 60℃;
With Chironomus riparius membrane-bound trehalase aq. acetate buffer;
With water; glycine; magnesium chloride at 70℃; aq. phosphate buffer;
With Arthrobacter sp. DL001 α-D-glucoside glucohydrolase; water at 30℃; for 0.5h; citrate-phosphate buffer; Enzymatic reaction;
With porcine kidney trehalase; water; citric acid Enzymatic reaction; Hydrolysis of trehalose and analogs Hydrolysis of trehalose and analogs was tested using porcine kidney trehalase (Sigma-Aldrich, T8778). The standard reaction was performed by adding 0.001 unit of trehalase into 50 μl reaction solution containing 135 mM citric acid (pH 5.7) and 28 mM trehalose or trehalose analogs. In addition, the inhibition of analog against the trehalase activity was also examined. The standard reaction was performed by adding 0.001 unit of trehalase into 50 μl reaction solution containing 135 mM citric acid (pH 5.7) and 44.8 mM α-D-lactulose, 44.8 mM α-D-melibiose, 0.2 μM validamycin A, or 0.2 μM validoxylamine A. Trehalase was incubated with analog for 30 min at 37° C., and the reaction was then started by addition of trehalose. After incubation at 37° C. for 2 hr, the reaction was terminated by heating the mixture in boiling water for 15 min. The activity of trehalase was assayed by measuring the amount of glucose produced from trehalose. The amount of carbohydrates after each enzymatic reaction was measured using a high-performance liquid chromatography (HPLC) system (Schambeck SFD 2100) equipped with an refractive index (RI) detector (SFD, RI 2000) at a flow rate of 1 ml/min. A carbohydrate analysis column (Shodex SUGAR SZ5532, 6.0 mm ID×150 mm L) equilibrated with 75% acetonitrile, 24% Milli-Q water, and 1% formic acid was used. The RI detector and column oven temperature were set to 40 and 60° C., respectively
With α-glucosidase; sodium acetate; sodium chloride In water at 37℃; Enzymatic reaction; Hydrolysis of maltooligosaccharides and various disaccharides General procedure: The initial velocities of the hydrolysis reactions performed using 2 mM concentrations of various substrates (maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose, maltoheptaose, maltooctaose, trehalose, kojibiose, and nigerose) were measured in the absence or presence of 300 mM NaCl under standard assay conditions. Enzyme concentrations used were 0.102 to 40.6 μg/mL. The initial velocity was expressed as the number of μmol of glucose released from the non-reducing end of the substrate per min per mg protein. When determining the hydrolysis rate for disaccharides, the concentration of liberated glucose was divided by two.
With water In ethanol at 200℃; for 0.138889h; Supercritical conditions; Isomerization or hydrolysis of saccharides in subcriticalaqueous ethanol General procedure: Isomerization of each saccharidewas carried out in a continuous reaction system, inwhich the feed saccharide solution was delivered usingan LC-10AD VP HPLC pump (Shimadzu, Kyoto,Japan), into a stainless steel tubular reactor (0.8 mmI.D. × 1.0 m length) heated in a temperature-controlledsilicone oil bath (Dow Corning Toray Silicone, Tokyo,Japan). Upon exiting the reactor, the effluent wasdirectly introduced to a stainless steel tube immersed inan ice water bath in order to quench the reaction. Thepressure inside the reactor was regulated at ca. 10 MPaand reduced to ambient after cooling using a back-pressurevalve (Upchurch Scientific Inc., Oak Harbor, WA,USA). The residence time was set in the range of 50-500 s. The reaction temperature was set at 180-220 °C.Ethanol concentration was adjusted from 0 to 80 wt%and the substrate feed concentration ranged from 0.5 to5 wt% for maltose isomerization. For other saccharides,the reaction temperature was set at 200 °C; ethanolconcentration was adjusted at 0 (subcritical water) and60 wt% and the feed concentration was 0.5 wt%

  • 29
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • C26H30O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 60℃; 1.A.1 Example 1: Synthesis of the compounds of the invention; A. Synthesis of sulfolipids [Show Image] 1. Benzylidenation of α,α-trehalose α,α-Trehalose dihydrate (1 eq.) was dehydrated by boiling in absolute ethanol (0.4 M) under reflux for 30 min. The dry residue 1 was then suspended in dry N,N-dimethylformamide (DMF, 0.4 M), and α,α-dimethoxytoluene (DMT, 2 eq.) was added, together with 10-camphorsulfonic acid (CSA, 0.05 eq.). The mixture was heated (60°C) during 1 h on a rotary evaporator with a light vacuum to eliminate the methanol. More DMT (0.25 eq.) and CSA (0.01 eq.) were then added and the mixture was attached again on the rotary evaporator. At the end of the reaction, DMF was evaporated. The mixture was stirred overnight in an aqueous sodium hydrogencarbonate solution (5 %) to give crystalline diacetal 2. The product was recrystallized by dissolution in boiling ethanol, addition of hot water, and slow cooling. Finally, the white crystals of 2 were filtered, washed with water and ether petroleum and dried (84 %).
  • 30
  • [ 99-20-7 ]
  • trehalose phosphorylase [ No CAS ]
YieldReaction ConditionsOperation in experiment
With Thermoanaerobacter brockii In water at 60℃; for 40h; Microbiological reaction; 1; 2 Experiment 1 Production of trehalose phosphorylase A culture medium was prepared according to the preparation procedure of Thermoanaerobacter brockii medium in "ATCC catalogue of Bacteria and Bacteriophages, 18th Edition" pp.452-456, published by American Type Culture Collection, 1992, except for replacing 0.5 %(w/v) glucose with 0.5 %(w/v) trehalose as a carbon source. Aliquots of 100 ml were placed in 100-ml pressure bottles, and seeded with Thermoanaerobacter brockii, ATCC 35047, followed by culturing at 60 °C for 48 hours for a seed culture. About 10 L of a fresh preparation of the same culture medium as used in the above seed culture were placed in four 11-L stainless-steel bottles, sterilized by heating, and then cooled to 60 °C and inoculated with one percent (v/v) of the seed culture, followed by culturing at 60 °C for about 40 hours. About 40 L of the resulting total cultures were centrifuged to obtain 92 grams(g) of cells. The cells were suspended in 10 mM phosphate buffer, ultrasonically crushed, and centrifuged to obtain a culture supernatant having the trehalose phosphorylase activity of 0.3 unit/ml. The supernatant was concentrated with a UF membrane to obtain an about 360 ml of enzyme concentrate having an activity of about 30 units/ml of trehalose phosphorylase. The activity of trehalose phosphorylase was assayed as follows: (1) Add a 0.2 ml of an enzyme solution to two milliliters of 20 mM phosphate buffer (pH 7.0) including 1.0 %(w/v) trehalose as a substrate, react the mixture solution at 60 °C for 30 min, and stop the enzymatic reaction by boiling a sampled 0.5 ml of the reaction mixture at 100 °C for 10 min; (2) admix 0.5 ml of a D-glucose oxidase/peroxidase reagent to the reaction mixture, allow to stand at 40 ° for 30 min, add 2.5 ml of 5 N hydrochloric acid to the mixture, and measure the absorbance at a wavelength of 525 nm; and (3) define one unit activity of trehalose phosphorylase as the enzyme amount that forms one micromole of D-glucose per minute under the above enzymatic reaction conditions. Experiment 2 Purification of trehalose phosphorylase Three hundred milliliters of the enzyme concentrate obtained in Experiment 1 was dialyzed against 10 mM phosphate buffer (pH 7.0) for 24 hours and centrifuged to remove insolubles. Three hundred and eighty milliliters (380 ml) of the obtained supernatant was subjected to an ion-exchange chromatography using 380 ml of "DEAE-TOYOPEARL 650" gel, commercialized by Tosoh Corporation, Tokyo, Japan. Trehalose phosphorylase was absorbed to "DEAE-TOYOPEARL 650" gel and eluted from the column with a linear gradient increasing from 0 M to 0.5 M of sodium chloride (a saline solution). Fractions, which were eluted at about 0.1 M of sodium chloride, were collected and further purified by the following method. The fractions were pooled and dialyzed against 10 mM phosphate buffer (pH 7.0) containing 1.5 M ammonium sulfate, and the dialyzed solution was centrifuged to remove insolubles, followed by subjecting to a hydrophobic column chromatography using 100 ml of "BUTYL-TOYOPEARL "650", a gel commercialized by Tosoh Corporation, Tokyo, Japan. In eluting with a linear gradient decreasing from 1.5 M to 0.5 M of ammonium sulfate, trehalose phosphorylase was eluted and collected as fractions with the enzyme activity. Further, the fractions were pooled and subjected to a gel filtration chromatography using 300 ml of "Ultrogel AcA44", a gel commercialized by Sepracor Co. , France, to collect fractions with the enzyme activity. The purified enzyme specimen had a yield of about 25 % for the aforesaid culture supernatant in terms of the activity of trehalose phosphorylase, and a specific activity of the purified trehalose phosphorylase, and specific activity of the purified enzyme sample was 78.2 units/mg protein. The purified enzyme was subjected to a gel electrophoresis containing 7.5 %(w/v) polyacrylamide to examine purity. The result showed that it was a relatively-high purified enzyme with an only one band.
  • 31
  • [ 99-20-7 ]
  • [ 6404-29-1 ]
  • [ 1206468-67-8 ]
YieldReaction ConditionsOperation in experiment
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 48h; 7-1 Example 7: Preparation of Trehalose Derivative having Eight Guanidine Groups<7-l> Introduction of Side Chain to Trehalose by AcylationTrehalose hydrate (0.87 g, 2.30 mmol), N-Boc-6-aminohexanoic acid (6.37 g, 27.55 mmol), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (5.81 g, 30.30 mmol) and 4-dimethylaminopyridine (0.84 g, 6.89 mmol) were dissolved in N,N-dimethylformamide (24 ml) and stirred at room temperature for 48 hours.After the completion of the reaction, the reaction mixture was subjected to azeotropic distillation along with toluene at 60 °C , diluted with ethyl acetate, and the extract was washed several times with saturated aqueous NaHCO3 and water. The organic layer thus obtained was dried over Na2SO4, concentrated under a reduced pressure, and then purified by column chromatography (ethyl acetate : hexane = 1 : 1) to obtain the title compound as a white solid (4.03 g).1H NMR (CDCl3) δ 1.24-1.66 (m, 120H, CH3 and NCH2CH2CH2CH2), 2.20-2.37 (m, 16H, CO-CH2), 3.08-3.21 (m, 16H, NCH2), 3.83-4.03 (m, 4H), 4.20-4.25 (m, 2H), 4.65-5.00 (m, 7H, NH), 5.01-5.09 (m, 4H), 5.29 (d, 2H, J=3.7 Hz, anomeric protons), 5.48 (app. t, 2H, J=9.7 Hz).
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 48h; 7.7-1 <7-1> Introduction of Side Chain to Trehalose by Acylation Trehalose hydrate (0.87 g, 2.30 mmol), N-Boc-6-aminohexanoic acid (6.37 g, 27.55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (5.81 g, 30.30 mmol) and 4-dimethylaminopyridine (0.84 g, 6.89 mmol) were dissolved in N,N-dimethylformamide (24 ml) and stirred at room temperature for 48 hours.After the completion of the reaction, the reaction mixture was subjected to azeotropic distillation along with toluene at 60° C., diluted with ethyl acetate, and the extract was washed several times with saturated aqueous NaHCO3 and water. The organic layer thus obtained was dried over Na2SO4, concentrated under a reduced pressure, and then purified by column chromatography (ethyl acetate:hexane=1:1) to obtain the title compound as a white solid (4.03 g).1H NMR (CDCl3) δ 1.24-1.66 (m, 120H, CH3 and NCH2CH2CH2CH2), 2.20-2.37 (m, 16H, CO-CH2), 3.08-3.21 (m, 16H, NCH2), 3.83-4.03 (m, 4H), 4.20-4.25 (m, 2H), 4.65-5.00 (m, 7H, NH), 5.01-5.09 (m, 4H), 5.29 (d, 2H, J=3.7 Hz, anomeric protons), 5.48 (app. t, 2H, J=9.7 Hz).
  • 32
  • [ 99-20-7 ]
  • [ 2524-64-3 ]
  • [ 1253891-13-2 ]
YieldReaction ConditionsOperation in experiment
39% With pyridine at 40℃; for 0.0333333h;
24% With pyridine for 18h;
24% With pyridine at 20℃; for 18h; 6-0-(diphenoxyphosphoryl)-D -trehalose (67)To a suspension of D-trehalose (7.50 g, 21 .9 mmol, 1 eq) in anhydrous pyridine (100 mL) was added dropwise diphenylchlorophosphate (4.54 mL, 21.9 mmol, 1 eq). TLC (1 :4:4, water/isopropanol/ethyl acetate) after 18 hours showed the presence of two products (desired product Rf 0.7). The reaction was quenched with methanol (10 mL). The reaction mixture was concentrated in vacuo, and the residue co-evaporated with toluene to remove pyridine. Silica gel chromatography (1 :3: 13 water/isopropanol/ethyl acetate) a l lowed separation of the two products. Lyophilization yielded the desired compound (3.02 g, 24%) as a white amorphous solid.[a]^2 +63.9 (c = 1.0 in MeOH); 1H NMR (500 MHz, METHANOL-^) δ ppm3.34 (1 H, at, J3,4 = 9.1 Hz, J4,5 = 9.1 Hz, H-4'), 3.38 (1 H, at, J3,4 = J4,5 = 9.1 Hz, H- 4), 3.43 (1 H, dd, J2,3 = 9.8 Hz, J = 3.5 Hz, H-2'), 3.48 (1 H, dd, J2,3 = 9.8 Hz, J = 3.8 Hz, H-2), 3.70 (1 H, dd, J6a,6b = 12.0 Hz, J5,6a = 5.4 Hz, H-6a'), 3.80 (1 H, at, J2,3 = J3,4 = 9.5 Hz, H-3'), 3.81 (1 H, t, J2,3 = J3_4 = 9.1 Hz, H-3), 3.80-3.86 (2 H, m, H-6b', H-5'), 4.09 (1 H, dt, J4,5 = 10.1 Hz, J5,6a = 2.1 Hz, J5,6b = 2.1 Hz, H-5), 4.48 (1 H, ddd, J6a,6b = H -5 Hz, Jp,6a = 7.1 Hz, J5,6a = 3.5Hz, H-6a), 4.55 (1 H, ddd, J6a,6b = 1 1.5 Hz, JP,6b 6.8 Hz, J5,6b = 1.9 Hz, H-6b), 5.09 (1 H, d, Jv,v = 3.8 Hz, H-l '), 5.10 (1 H, d, J,2 = 3.8 Hz, H-l), 7.21-7.31 (3 H, m, Ar-Hortho, Ar-Hpara), 7.40-7.43 (2 H, m, Ar-Hmeta); 13C NMR (126 MHz, METHANOL-;/) δ ppm 62.6 (C-6'), 69.8 (1 C, d, JP,6 = 6.7 Hz, C-6), 71.2 (C-4'), 71.9 (C-4), 72.0 (1 C, d, JP,5 = 6.7 Hz, C-5), 73.0 (C-5'), 73.2 (C- 2'), 73.9 (C-2), 74.4 (C-3'), 74.6 (C-3), 95.2 (C-L), 95.3 (C-l), 121.4 (2 C, d, JP,C = 4.8 Hz, Ar-Cortho), 126.8 (Ar-Cpara), 131.1 (Ar-Cmeta), 151.9 (1 C, d, JP,C = 7.6 Hz, Ar- Cipso), 151.9 (1 C, d, JP,C = 7.6 Hz, Ar-CipS0); 31P(1H) NMR (162 MHz, METHANOL- d) <5ppm -11.9; IR (KBr disc): v = 1287 (P=0), 3271 br (OH) cm-1; (ESI+) m/z 596.74 (M+Na+); HRMS (ESI+) m/z calcd. for C24H3iOi4P (M+Na+): 596.1344. Found: 596.1357.
24% With pyridine at 20℃; for 18h;
24% With pyridine; dmap at 20℃; for 3h;

  • 33
  • [ 69-79-4 ]
  • [ 1109-28-0 ]
  • [ 3371-50-4 ]
  • [ 7485-51-0 ]
  • [ 99-20-7 ]
  • [ 50-99-7 ]
  • [ 499-40-1 ]
YieldReaction ConditionsOperation in experiment
In water; at 40℃;pH 6.0;Acetate buffer; Enzymatic reaction;Reactivity; Experiment 12-1Product from Maltose by the Enzyme ReactionAqueous maltose solution and acetate buffer (pH 6.0) were mixed to give final concentrations of 1percent (w/v) and 10 mM, respectively, to make into a substrate solution. The substrate solution was admixed with 10 units/g-solid substrate of alpha-glucosyltransferase, obtained by the method in Experiment 6, and followed by the enzyme reaction at 40° C. and pH 6.0. Aliquots were sampled from the reaction mixture with time and the reaction was stopped by keeping at 100° C. for 10 min. The saccharide compositions of the samples were measured by HPLC and GC. HPLC and GC were carried out under the conditions described in Experiment 4-2. The results are in Table 10. TABLE 10 Reaction Saccharide Composition (percent, w/w) Time DP1 DP2 DP3 (hr) Glucose Maltose Isomaltose Neotrehalose Maltotriose Panose Isopanose Isomaltotriose DP4 DP5 DP6 0 0.0 99.2 0.0 0.0 0.8 0.0 0.0 0.0 0.0 0.0 0.0 1 12.1 55.0 0.7 0.0 13.2 16.1 0.0 0.0 2.9 0.0 0.0 2 18.4 33.5 1.0 0.0 14.4 24.1 0.0 0.0 7.6 1.0 0.0 4 23.7 17.3 2.5 0.0 10.0 29.3 0.0 0.0 13.0 4.2 0.0 8 27.0 10.4 4.7 0.0 4.9 27.8 0.0 0.0 15.9 5.3 4.0 24 30.4 6.0 10.0 2.6 1.4 11.0 1.0 3.6 15.3 10.2 8.5 48 31.5 6.2 13.8 3.9 0.7 4.1 1.5 4.2 12.4 10.3 11.4 DP: Glucose polymerization degreeAs is evident from the results in Table 10, at initial stage (after one hour) of the reaction, glucose, maltotriose, and panose were formed as major reaction products from the substrate, maltose, by the action of the alpha-glucosyltransferase of the present invention. Also, oligosaccharides with a glucose polymerization degree of 4 and 5 were formed when the reaction time was elapsed 2 to 4 hours. Accompanying with the progress of the reaction, the content of maltotriose reached a maximum, 14.4percent, at 2 hours and then decreased; and the content of panose reached a maximum, 29.3percent at 4 hours and then decreased; and the content of isomaltose was increased with the decrease of the contents of maltotriose and panose. Further, the contents of isomaltose and oligosaccharides with a glucose polymerization degree of 4 or higher were increased until 48 hours.From these results, it was revealed that the alpha-glucosyltransferase of the present invention acts on maltose and forms glucose, maltotriose, and panose by catalyzing both alpha-1,4 and alpha-1,6 glucosyl transfer at initial stage of the reaction; and forms isomaltose, which is formed by alpha-1,6 glucosyl transfer to glucose, and isopanose and isomaltotriose, which are formed by alpha-1,4 and alpha-1,6 glucosyl transfer to isomaltose accompanied with the progress of the reaction. Since the identification of many kinds of oligosaccharide with glucose polymerization degree of 4 or higher is difficult in this experiment, the reaction mechanism of the enzyme was investigated in the following Experiment 12-2 using maltopentaose, whose glucose polymerization degree is higher than maltose, as substrate.
  • 34
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 1239971-78-8 ]
YieldReaction ConditionsOperation in experiment
96% Stage #1: TREHALOSE With palladium 10% on activated carbon; hydrogen; water-d2 at 80℃; for 72h; Stage #2: acetic anhydride With pyridine at 20℃; for 24h; regioselective reaction;
  • 35
  • [ 99-20-7 ]
  • [ 58479-61-1 ]
  • [ 1253891-15-4 ]
  • [ 1138027-97-0 ]
YieldReaction ConditionsOperation in experiment
1: 44% 2: 10% With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 26h;
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 36h; 6,6'-0-Di-tertbutyldiphenylsilyl-2,3,4,2',3 ',4'-hexa-0-benzyl- a,a -D-trehalose (56); To a stirred suspension of D-trehalose (2 g, 5.85 mmol, 1 eq) and imidazole (0.39 g, 5 .29 mmol, 0.9 eq) in dry DMF (10 mL) was added tert-butyl diphenylchlorosilane (TBDPS-Cl) (3 mL, 11.5 mmol, 2.0 eq ) at RT. After stirring for 36 hours, TLC (2: 1 ethyl acetate/methanol), indicated the complete consumption of starting materials and the formation of the product (Rf 0.35) as well as the mono TBDPS-trehalose (Rf 0.2). The reaction mixture was concentrated in vacuo and purification attained via silica gel chromatography (2: 1, ethyl acetate/isopropanol) to give the desired product as a mixture of mono and di-TBDPS protected compounds and a white solid. (2.3 g, 55%), which were used without further purification. This mixture was dissolved in anhydrous DMF (25 mL), and sodium hydride (60% dispersed in mineral oil) (700 mg, 29.1 mmol) was added portionwise for a period of 10 min at 0 °C. Benzyl bromide (2 mL, 11.6 mmol, 6 eq) was then added dropwise and the mixture left to stir under an atmosphere of argon at room temperature. After an 18 h period, TLC (5: 1 petrol/ethyl acetate) indicated the formation of product (Rf 0.9) with complete consumption of the starting material (Rf 0). The reaction mixture was quenched by the slow addition of methanol (150 mL) and stirred for 30 min, at which point the resulting solution was concentrated in vacuo. The residue was dissolved in DCM (800 mL), washed with water and brine, filtered and concentrated in vacuo. Purification by column column chromatography (petrol/ethyl acetate, 10: 1) afforded 56 and 57 as a 2: 1 mixture of products (by NMR), which were not fully separated (2.987 g, 41% over two steps) as a viscous clear oil. Further column chromatography yielded the titled compound (300 mg, 5% over two steps); [α]^ + 23.6 (c = 1.0 in CHC13); 1H NMR (400 MHz, CHLOROFORM-;/) δ ppm 1.28 (18 H, s, 2 x C (CH3)), 3.75 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.8 Hz, H-2, H-2'), 3.79 (2 H, dd, J6a,6b = 10.5 Hz, J5_6b = 1.8 Hz, H-6b, H-6b'), 3.92 (2 H, dd, J6a,6b = 10.6 Hz, J5 = 2.8 Hz, H-6a, H-6a'), 4.03 (2 H, at, J3,4 = J 4,5 = 9.6 Hz, H-4, H-4'), 4.18 - 4.28 (4 H, m, H-5, H-5', H-3,H-3'), 4.72 (2 H, d, J = 11.8 Hz, 2 x OCH2Ph), 4.80 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.89 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 5.04 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.10 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.15 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.39 (2 H, d, Ju = 3.5 Hz, H-l, H-l '), 7.13 - 7.63 (40 H, m, Ar-H) 7.79 - 7.93 (10 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 19.5 (6 C, s, 3 x C(CH3)3), 27.0 (2 C, s, 2 x C(CH3)3), 65.6 (2 C, C-6, C-6'), 71.7 (2 C, C-5, C- 5'), 72.9 (2 C, OCH2Ph), 75.3 (2 C, OCH2Ph), 76.0 (2 C, OCH2Ph), 77.7 (2 C, C-4, C-4'), 80.3 (2 C, C-2, C-2'), 82.1 (2 C, C-3, C-3'), 94.2 (2 C, C-l, C-l '), 126.1, 127.0, 127.2, 127.4, 127.7, 127.7, 127.8, 127.9, 128.0, 128.1, 128.3, 128.3, 128.6, 128.9, 129.2, 129.8, 129.9, 133.5, 133.6, 133.7, 135.6, 135.8, (6 x OCH2Ph, 4 x OTBDPS), 137.9, 138.2, 138.4, 138.7, 138.9, (10 C, 6 x 1 C, OCH2Ph, 4 x 1 C, OTBDPS ); IR (thin film): v = 3069.3, 2930.1, 2856.3 (C=CH), 1453.7, 1427.6, (C=C), 1219.4, 111.2, 1069.3, 1027.4, 824.0, 772.5 cm"1 m/z (ES+) 1376.6 (M + NH4+). Isotopic distribution: Species observed (M+Na+), peaks observed 1381.59 (91.5%), 1382.59 (100%), 1383.59 (48.3%), 1384.59 (17.8%), 1385.60 (5.8%), 1386.59 (1.7%) peaks calculated 1381.62 (95.5%), 1382.62 (100%), 1383.62 (59.8%), 1384.62 (25.3%), 1385.63 (8.0%).
With 1H-imidazole In N,N-dimethyl-formamide at 20℃;
  • 36
  • [ 99-20-7 ]
  • [ 3033-77-0 ]
  • C24H50N2O13(2+)*2Cl(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With sodium chloride; sodium hydroxide In isopropyl alcohol at 20 - 40℃; for 7h;
  • 37
  • [ 99-20-7 ]
  • [ 79-11-8 ]
  • C16H24O15(2-)*2Na(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
94.8% Stage #1: TREHALOSE With sodium hydroxide In isopropyl alcohol at 20℃; for 0.666667h; Stage #2: chloroacetic acid In isopropyl alcohol at 40℃; for 3h;
  • 38
  • [ 99-20-7 ]
  • [ 100-39-0 ]
  • [ 142-61-0 ]
  • [ 58479-61-1 ]
  • [ 1274878-20-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE; tert-butylchlorodiphenylsilane With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 36h; Stage #2: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #3: benzyl bromide; Hexanoyl chloride 6,6'-0-Di-tertbutyldiphenylsilyl-2,3,4,2',3 ',4'-hexa-0-benzyl- a,a -D-trehalose (56); To a stirred suspension of D-trehalose (2 g, 5.85 mmol, 1 eq) and imidazole (0.39 g, 5 .29 mmol, 0.9 eq) in dry DMF (10 mL) was added tert-butyl diphenylchlorosilane (TBDPS-Cl) (3 mL, 11.5 mmol, 2.0 eq ) at RT. After stirring for 36 hours, TLC (2: 1 ethyl acetate/methanol), indicated the complete consumption of starting materials and the formation of the product (Rf 0.35) as well as the mono TBDPS-trehalose (Rf 0.2). The reaction mixture was concentrated in vacuo and purification attained via silica gel chromatography (2: 1, ethyl acetate/isopropanol) to give the desired product as a mixture of mono and di-TBDPS protected compounds and a white solid. (2.3 g, 55%), which were used without further purification. This mixture was dissolved in anhydrous DMF (25 mL), and sodium hydride (60% dispersed in mineral oil) (700 mg, 29.1 mmol) was added portionwise for a period of 10 min at 0 °C. Benzyl bromide (2 mL, 11.6 mmol, 6 eq) was then added dropwise and the mixture left to stir under an atmosphere of argon at room temperature. After an 18 h period, TLC (5: 1 petrol/ethyl acetate) indicated the formation of product (Rf 0.9) with complete consumption of the starting material (Rf 0). The reaction mixture was quenched by the slow addition of methanol (150 mL) and stirred for 30 min, at which point the resulting solution was concentrated in vacuo. The residue was dissolved in DCM (800 mL), washed with water and brine, filtered and concentrated in vacuo. Purification by column column chromatography (petrol/ethyl acetate, 10: 1) afforded 56 and 57 as a 2: 1 mixture of products (by NMR), which were not fully separated (2.987 g, 41% over two steps) as a viscous clear oil. Further column chromatography yielded the titled compound (300 mg, 5% over two steps); [α]^ + 23.6 (c = 1.0 in CHC13); 1H NMR (400 MHz, CHLOROFORM-;/) δ ppm 1.28 (18 H, s, 2 x C (CH3)), 3.75 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.8 Hz, H-2, H-2'), 3.79 (2 H, dd, J6a,6b = 10.5 Hz, J5_6b = 1.8 Hz, H-6b, H-6b'), 3.92 (2 H, dd, J6a,6b = 10.6 Hz, J5 = 2.8 Hz, H-6a, H-6a'), 4.03 (2 H, at, J3,4 = J 4,5 = 9.6 Hz, H-4, H-4'), 4.18 - 4.28 (4 H, m, H-5, H-5', H-3,H-3'), 4.72 (2 H, d, J = 11.8 Hz, 2 x OCH2Ph), 4.80 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.89 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 5.04 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.10 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.15 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.39 (2 H, d, Ju = 3.5 Hz, H-l, H-l '), 7.13 - 7.63 (40 H, m, Ar-H) 7.79 - 7.93 (10 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 19.5 (6 C, s, 3 x C(CH3)3), 27.0 (2 C, s, 2 x C(CH3)3), 65.6 (2 C, C-6, C-6'), 71.7 (2 C, C-5, C- 5'), 72.9 (2 C, OCH2Ph), 75.3 (2 C, OCH2Ph), 76.0 (2 C, OCH2Ph), 77.7 (2 C, C-4, C-4'), 80.3 (2 C, C-2, C-2'), 82.1 (2 C, C-3, C-3'), 94.2 (2 C, C-l, C-l '), 126.1, 127.0, 127.2, 127.4, 127.7, 127.7, 127.8, 127.9, 128.0, 128.1, 128.3, 128.3, 128.6, 128.9, 129.2, 129.8, 129.9, 133.5, 133.6, 133.7, 135.6, 135.8, (6 x OCH2Ph, 4 x OTBDPS), 137.9, 138.2, 138.4, 138.7, 138.9, (10 C, 6 x 1 C, OCH2Ph, 4 x 1 C, OTBDPS ); IR (thin film): v = 3069.3, 2930.1, 2856.3 (C=CH), 1453.7, 1427.6, (C=C), 1219.4, 111.2, 1069.3, 1027.4, 824.0, 772.5 cm"1 m/z (ES+) 1376.6 (M + NH4+). Isotopic distribution: Species observed (M+Na+), peaks observed 1381.59 (91.5%), 1382.59 (100%), 1383.59 (48.3%), 1384.59 (17.8%), 1385.60 (5.8%), 1386.59 (1.7%) peaks calculated 1381.62 (95.5%), 1382.62 (100%), 1383.62 (59.8%), 1384.62 (25.3%), 1385.63 (8.0%).; ',3 ',4'-Hexa-0-benzyl- a,a -D-trehalose (58)The 2: 1 mixture of 56 and 57 (l .Olg, 0.83 mmol) was dissolved in DMF (lOmL) and to this was added TBAF dropwise (70%> in H20) (1 mL, 2.87 mmol, 3.5 eq). Reaction was stirred for 3 h at 60 °C. TLC (2: 1 petrol/ethyl acetate) indicated products (Rf 0.4) and (Rf 0.05) and complete consumption of starting material (Rf 1.0). Crude product was washed with satd brine and NaHC03, extracted into dichloromethane and concentrated in vacuo. Purification by column chromatography (2: 1 petrol/ethyl acetate followed by 1 : 1 petrol/ethyl acetate and ethyl acetate) yielded 58 (202.5 mg, 36%, based on 2: 1 ratio of starting material) as a clear oil and 59 (156 mg, 58% based on 2: 1 ratio of starting material) and recovered starting material (130 mg, 7%). Combined yield of both products was 61%>.[3) [Lit. [ag +104 (c = 1.6 in CHC13)]21; 1H NMR (400 MHz, CHLOROFORM- ) δ ppm 3.55 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.1 Hz, H-2, H-2'), 3.59-3.64 (6 H, m, H-6a, H-6a', H-6b, H-6b'), 3.61 (2 H, at, J3,4 = J4,s = 10.1 Hz, H-4, H-4'), 4.05 - 4.13 (4 H, m, H-3, H-3', H-5, H-5'), 4.67 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 4.68 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.73 (2 H, d, J =11.9 Hz, 2 x OCH2Ph), 4.90 (2H, d, J =10.9 Hz, 2 x OCH2Ph), 4.91 (2 H, d, J =11.4 Hz, 2 x OCH2Ph), 5.02 (2 H, d, J=10.8 Hz, 2 x OCH2Ph), 5.16 (2 H, d, Ju = 3.8 Hz, H-l, H- 1), 7.15 - 7.52 (30 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 61.4 (2 C, C-6, C-6'), 71.4 (2 C, C-5, C-5'), 72.9 (2 C, 2 x OCH2Ph), 75.0 (2 C, 2 x OCH2Ph), 75.6 (1 C, 2 x OCH2Ph), 76.7 (2 C, s, C-4, C-4'), 79.4 (2 C, C-2, C-2'), 81.6 (2 C, C-3, C-3'), 93.9 (2 C, C-l, C-l '), 123.8, 127.5, 127.6, 127.7, 127.9, 128.1, 128.4, 128.5 (6 x OCH2Ph), 138.0, 138.2, 138.7 (6 x 1 C, 6 x OCH2Ph); MS m/z (ESI+) 900.4 (M + NH4+).; 6,6'-Dihexanoyl-0-2,3, ',3 ',4'-hexa-0-benzyl-a,a-D-trehalose (61)58 (1 g, 1.13 mmol, 1 eq) was dissolved in anhydrous pyridine (2 mL) and to this was added hexanoyl chloride (0.5 mL, 3.8 mmol, 3.3 eq). Reaction was stirred for 30 min at RT upon which time TLC (2: 1 petrol/ethyl acetate) indicated complete conversion from starting material (Rf 0.05) to product (Rf 0.9). Reaction was washed with satd. NaHC03 solution and concentrated in vacuo. Column chromatography (10: 1 petrol/ ethyl acetate, 1% triethylamine) yielded the desired product as a clear oil(1 .12g, 91 %). [ag + 75.6 (c = 0.39 in CHC13); 1H NMR (400 MHz , CHLOROFORM- ) δ ppm 0.86 (6 H, t, J = 6.9 Hz, 2 x OCO(CH2)4CH3_), 1.23 - 1.29 (8 H, m, 2 x OCO(CH2)2(CH2)2CH3), 1.54 - 1.65 (8 H, m, 2 x OCO(CH2)2(CH2)2CH3), 3.54 (4 H, at, J3,4 = J4,s = 9.6 Hz, H-4, H-4'), 3.57 (4 H, dd, J2.3 = 9.6 Hz, Ju = 3.5 Hz, H-2, H-2'), 4.06 (4 H, at, J2,3 = Js,4 = 9.3 Hz, H-3, H-3'), 4.06 (4 H, dd, J6a,6b = 12.3 Hz, J5 = 2.0 Hz, H-6a, H-6a'), 4.16 (2 H, dd, J6a,6b = 12.3 Hz, JSi6b = 3.3 Hz H-6b, H-6b'), 4.24 (2 H, ddd, J4,s = 10.0 Hz, JSi6b = 3.4 Hz, J5,6a = 2.0 Hz, H-5, H-5'), 4.53 (2 H, d, J = 10.6 Hz, OCH2Ph), 4.69 (2 H, d, J = 12.1 Hz, OCH2Ph), 4.73 (2 H, d, J = 11.9 Hz, OCH2Ph), 4.88 (4 H, d, J = 10.6 Hz, OCH2Ph), 4.88 (3 H, d, J = 10.9 Hz, OCH2Ph), 5.02 (2 H, d, J = 10.6 Hz, OCH2Ph), 5.18 (2 H, d, J;,2 = 3.5 Hz, H-l, H-l '), 7.04 - 7.51 (40 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 13.9 (2 C, OCO(CH2)4CH3), 22.3 (2 C, OCO(CH2)4CH2CH3), 24.5 (2 C, OCO(CH2)4CH2CH2CH3), 31.3 (2 C, OCOCH2CH2 (CH2)2CH3), 34.0 (2 C, OCOCH2(CH2)3CH3), 62.5 (2 C, C-6, C-6'), 69.1 (2 C, C-5, C-5'), 72.9 (2 C, OCH2Ph), 75.2 (4 C, 2 x OCH2Ph), 75.7 (2 C, OCH2Ph), 77.4 (2 C, C-4, C-4'), 79.2 (2 C, C-2, C-2'), 81.6 (2 C, C-3, C-3'), 94.0 (2 C, C-l, C-l '), 127.5, 127.7, 127.8, 127.9, 128.1, 128.4, 128.4 (6 x OCH2Ph); 137.8, 137.8, 138.5 (6 x 1 C = 6 x OCH2Ph); 173.5 (2 C, 2 x C=0); IR (thin film): v = 3419 br (OH), 2956, 2925, 2854 (C=CH), 1733 (C=0), 1637, 1456 (C=C), 1219, 1 177, 1 150, 1 101, 1078, 1053, 1026, 990, 772 cm"1; MS mlz (ESI+) 1096.5 (M+NH4); Isotopic distribution: Species observed (M+Na+), peaks observed 1101.53 (100%), 1102.53 (72.8%), 1103.54 (28.8%), 1104.54 (8.1%), 1105.54 (1.8%), peaks calculated 1101.52 (100%), 1102.52 (74.4%), 1103.53 (30.0%), 1104.53 (8.3%), 1105.53 (1.9%), 1105.49 (1.4%).
  • 39
  • [ 99-20-7 ]
  • [ 100-39-0 ]
  • [ 58479-61-1 ]
  • [ 1253692-53-3 ]
  • [ 1253692-54-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE; tert-butylchlorodiphenylsilane With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 36h; Stage #2: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #3: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 18h; Inert atmosphere; 6,6'-0-Di-tertbutyldiphenylsilyl-2,3,4,2',3 ',4'-hexa-0-benzyl- a,a -D-trehalose (56); To a stirred suspension of D-trehalose (2 g, 5.85 mmol, 1 eq) and imidazole (0.39 g, 5 .29 mmol, 0.9 eq) in dry DMF (10 mL) was added tert-butyl diphenylchlorosilane (TBDPS-Cl) (3 mL, 11.5 mmol, 2.0 eq ) at RT. After stirring for 36 hours, TLC (2: 1 ethyl acetate/methanol), indicated the complete consumption of starting materials and the formation of the product (Rf 0.35) as well as the mono TBDPS-trehalose (Rf 0.2). The reaction mixture was concentrated in vacuo and purification attained via silica gel chromatography (2: 1, ethyl acetate/isopropanol) to give the desired product as a mixture of mono and di-TBDPS protected compounds and a white solid. (2.3 g, 55%), which were used without further purification. This mixture was dissolved in anhydrous DMF (25 mL), and sodium hydride (60% dispersed in mineral oil) (700 mg, 29.1 mmol) was added portionwise for a period of 10 min at 0 °C. Benzyl bromide (2 mL, 11.6 mmol, 6 eq) was then added dropwise and the mixture left to stir under an atmosphere of argon at room temperature. After an 18 h period, TLC (5: 1 petrol/ethyl acetate) indicated the formation of product (Rf 0.9) with complete consumption of the starting material (Rf 0). The reaction mixture was quenched by the slow addition of methanol (150 mL) and stirred for 30 min, at which point the resulting solution was concentrated in vacuo. The residue was dissolved in DCM (800 mL), washed with water and brine, filtered and concentrated in vacuo. Purification by column column chromatography (petrol/ethyl acetate, 10: 1) afforded 56 and 57 as a 2: 1 mixture of products (by NMR), which were not fully separated (2.987 g, 41% over two steps) as a viscous clear oil. Further column chromatography yielded the titled compound (300 mg, 5% over two steps); [α]^ + 23.6 (c = 1.0 in CHC13); 1H NMR (400 MHz, CHLOROFORM-;/) δ ppm 1.28 (18 H, s, 2 x C (CH3)), 3.75 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.8 Hz, H-2, H-2'), 3.79 (2 H, dd, J6a,6b = 10.5 Hz, J5_6b = 1.8 Hz, H-6b, H-6b'), 3.92 (2 H, dd, J6a,6b = 10.6 Hz, J5 = 2.8 Hz, H-6a, H-6a'), 4.03 (2 H, at, J3,4 = J 4,5 = 9.6 Hz, H-4, H-4'), 4.18 - 4.28 (4 H, m, H-5, H-5', H-3,H-3'), 4.72 (2 H, d, J = 11.8 Hz, 2 x OCH2Ph), 4.80 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.89 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 5.04 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.10 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.15 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.39 (2 H, d, Ju = 3.5 Hz, H-l, H-l '), 7.13 - 7.63 (40 H, m, Ar-H) 7.79 - 7.93 (10 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 19.5 (6 C, s, 3 x C(CH3)3), 27.0 (2 C, s, 2 x C(CH3)3), 65.6 (2 C, C-6, C-6'), 71.7 (2 C, C-5, C- 5'), 72.9 (2 C, OCH2Ph), 75.3 (2 C, OCH2Ph), 76.0 (2 C, OCH2Ph), 77.7 (2 C, C-4, C-4'), 80.3 (2 C, C-2, C-2'), 82.1 (2 C, C-3, C-3'), 94.2 (2 C, C-l, C-l '), 126.1, 127.0, 127.2, 127.4, 127.7, 127.7, 127.8, 127.9, 128.0, 128.1, 128.3, 128.3, 128.6, 128.9, 129.2, 129.8, 129.9, 133.5, 133.6, 133.7, 135.6, 135.8, (6 x OCH2Ph, 4 x OTBDPS), 137.9, 138.2, 138.4, 138.7, 138.9, (10 C, 6 x 1 C, OCH2Ph, 4 x 1 C, OTBDPS ); IR (thin film): v = 3069.3, 2930.1, 2856.3 (C=CH), 1453.7, 1427.6, (C=C), 1219.4, 111.2, 1069.3, 1027.4, 824.0, 772.5 cm"1 m/z (ES+) 1376.6 (M + NH4+). Isotopic distribution: Species observed (M+Na+), peaks observed 1381.59 (91.5%), 1382.59 (100%), 1383.59 (48.3%), 1384.59 (17.8%), 1385.60 (5.8%), 1386.59 (1.7%) peaks calculated 1381.62 (95.5%), 1382.62 (100%), 1383.62 (59.8%), 1384.62 (25.3%), 1385.63 (8.0%).
300 mg Stage #1: TREHALOSE; tert-butylchlorodiphenylsilane With 1H-imidazole In N,N-dimethyl-formamide at 20℃; Stage #2: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Stage #3: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere;
  • 40
  • [ 99-20-7 ]
  • [ 100-39-0 ]
  • [ 58479-61-1 ]
  • [(2R,3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-((2R,3R,4S,5R,6R)-3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl]-methanol [ No CAS ]
  • [ 103128-35-4 ]
YieldReaction ConditionsOperation in experiment
1: 36% 2: 58% Stage #1: TREHALOSE; tert-butylchlorodiphenylsilane With 1H-imidazole In N,N-dimethyl-formamide at 20℃; Stage #2: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Stage #3: benzyl bromide Further stages;
Stage #1: TREHALOSE; tert-butylchlorodiphenylsilane With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 36h; Stage #2: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #3: benzyl bromide 6,6'-0-Di-tertbutyldiphenylsilyl-2,3,4,2',3 ',4'-hexa-0-benzyl- a,a -D-trehalose (56); To a stirred suspension of D-trehalose (2 g, 5.85 mmol, 1 eq) and imidazole (0.39 g, 5 .29 mmol, 0.9 eq) in dry DMF (10 mL) was added tert-butyl diphenylchlorosilane (TBDPS-Cl) (3 mL, 11.5 mmol, 2.0 eq ) at RT. After stirring for 36 hours, TLC (2: 1 ethyl acetate/methanol), indicated the complete consumption of starting materials and the formation of the product (Rf 0.35) as well as the mono TBDPS-trehalose (Rf 0.2). The reaction mixture was concentrated in vacuo and purification attained via silica gel chromatography (2: 1, ethyl acetate/isopropanol) to give the desired product as a mixture of mono and di-TBDPS protected compounds and a white solid. (2.3 g, 55%), which were used without further purification. This mixture was dissolved in anhydrous DMF (25 mL), and sodium hydride (60% dispersed in mineral oil) (700 mg, 29.1 mmol) was added portionwise for a period of 10 min at 0 °C. Benzyl bromide (2 mL, 11.6 mmol, 6 eq) was then added dropwise and the mixture left to stir under an atmosphere of argon at room temperature. After an 18 h period, TLC (5: 1 petrol/ethyl acetate) indicated the formation of product (Rf 0.9) with complete consumption of the starting material (Rf 0). The reaction mixture was quenched by the slow addition of methanol (150 mL) and stirred for 30 min, at which point the resulting solution was concentrated in vacuo. The residue was dissolved in DCM (800 mL), washed with water and brine, filtered and concentrated in vacuo. Purification by column column chromatography (petrol/ethyl acetate, 10: 1) afforded 56 and 57 as a 2: 1 mixture of products (by NMR), which were not fully separated (2.987 g, 41% over two steps) as a viscous clear oil. Further column chromatography yielded the titled compound (300 mg, 5% over two steps); [α]^ + 23.6 (c = 1.0 in CHC13); 1H NMR (400 MHz, CHLOROFORM-;/) δ ppm 1.28 (18 H, s, 2 x C (CH3)), 3.75 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.8 Hz, H-2, H-2'), 3.79 (2 H, dd, J6a,6b = 10.5 Hz, J5_6b = 1.8 Hz, H-6b, H-6b'), 3.92 (2 H, dd, J6a,6b = 10.6 Hz, J5 = 2.8 Hz, H-6a, H-6a'), 4.03 (2 H, at, J3,4 = J 4,5 = 9.6 Hz, H-4, H-4'), 4.18 - 4.28 (4 H, m, H-5, H-5', H-3,H-3'), 4.72 (2 H, d, J = 11.8 Hz, 2 x OCH2Ph), 4.80 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.89 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 5.04 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.10 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.15 (2 H, d, J = 10.6 Hz, 2 x OCH2Ph), 5.39 (2 H, d, Ju = 3.5 Hz, H-l, H-l '), 7.13 - 7.63 (40 H, m, Ar-H) 7.79 - 7.93 (10 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 19.5 (6 C, s, 3 x C(CH3)3), 27.0 (2 C, s, 2 x C(CH3)3), 65.6 (2 C, C-6, C-6'), 71.7 (2 C, C-5, C- 5'), 72.9 (2 C, OCH2Ph), 75.3 (2 C, OCH2Ph), 76.0 (2 C, OCH2Ph), 77.7 (2 C, C-4, C-4'), 80.3 (2 C, C-2, C-2'), 82.1 (2 C, C-3, C-3'), 94.2 (2 C, C-l, C-l '), 126.1, 127.0, 127.2, 127.4, 127.7, 127.7, 127.8, 127.9, 128.0, 128.1, 128.3, 128.3, 128.6, 128.9, 129.2, 129.8, 129.9, 133.5, 133.6, 133.7, 135.6, 135.8, (6 x OCH2Ph, 4 x OTBDPS), 137.9, 138.2, 138.4, 138.7, 138.9, (10 C, 6 x 1 C, OCH2Ph, 4 x 1 C, OTBDPS ); IR (thin film): v = 3069.3, 2930.1, 2856.3 (C=CH), 1453.7, 1427.6, (C=C), 1219.4, 111.2, 1069.3, 1027.4, 824.0, 772.5 cm"1 m/z (ES+) 1376.6 (M + NH4+). Isotopic distribution: Species observed (M+Na+), peaks observed 1381.59 (91.5%), 1382.59 (100%), 1383.59 (48.3%), 1384.59 (17.8%), 1385.60 (5.8%), 1386.59 (1.7%) peaks calculated 1381.62 (95.5%), 1382.62 (100%), 1383.62 (59.8%), 1384.62 (25.3%), 1385.63 (8.0%).; ',3 ',4'-Hexa-0-benzyl- a,a -D-trehalose (58)The 2: 1 mixture of 56 and 57 (l .Olg, 0.83 mmol) was dissolved in DMF (lOmL) and to this was added TBAF dropwise (70%> in H20) (1 mL, 2.87 mmol, 3.5 eq). Reaction was stirred for 3 h at 60 °C. TLC (2: 1 petrol/ethyl acetate) indicated products (Rf 0.4) and (Rf 0.05) and complete consumption of starting material (Rf 1.0). Crude product was washed with satd brine and NaHC03, extracted into dichloromethane and concentrated in vacuo. Purification by column chromatography (2: 1 petrol/ethyl acetate followed by 1 : 1 petrol/ethyl acetate and ethyl acetate) yielded 58 (202.5 mg, 36%, based on 2: 1 ratio of starting material) as a clear oil and 59 (156 mg, 58% based on 2: 1 ratio of starting material) and recovered starting material (130 mg, 7%). Combined yield of both products was 61%>.[3) [Lit. [ag +104 (c = 1.6 in CHC13)]21; 1H NMR (400 MHz, CHLOROFORM- ) δ ppm 3.55 (2 H, dd, J2,3 = 9.8 Hz, Ju = 3.1 Hz, H-2, H-2'), 3.59-3.64 (6 H, m, H-6a, H-6a', H-6b, H-6b'), 3.61 (2 H, at, J3,4 = J4,s = 10.1 Hz, H-4, H-4'), 4.05 - 4.13 (4 H, m, H-3, H-3', H-5, H-5'), 4.67 (2 H, d, J = 10.9 Hz, 2 x OCH2Ph), 4.68 (2 H, d, J = 11.9 Hz, 2 x OCH2Ph), 4.73 (2 H, d, J =11.9 Hz, 2 x OCH2Ph), 4.90 (2H, d, J =10.9 Hz, 2 x OCH2Ph), 4.91 (2 H, d, J =11.4 Hz, 2 x OCH2Ph), 5.02 (2 H, d, J=10.8 Hz, 2 x OCH2Ph), 5.16 (2 H, d, Ju = 3.8 Hz, H-l, H- 1), 7.15 - 7.52 (30 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 61.4 (2 C, C-6, C-6'), 71.4 (2 C, C-5, C-5'), 72.9 (2 C, 2 x OCH2Ph), 75.0 (2 C, 2 x OCH2Ph), 75.6 (1 C, 2 x OCH2Ph), 76.7 (2 C, s, C-4, C-4'), 79.4 (2 C, C-2, C-2'), 81.6 (2 C, C-3, C-3'), 93.9 (2 C, C-l, C-l '), 123.8, 127.5, 127.6, 127.7, 127.9, 128.1, 128.4, 128.5 (6 x OCH2Ph), 138.0, 138.2, 138.7 (6 x 1 C, 6 x OCH2Ph); MS m/z (ESI+) 900.4 (M + NH4+).
  • 41
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 18162-48-6 ]
  • [ 1274878-75-9 ]
  • [ 1274878-77-1 ]
  • [ 25018-27-3 ]
YieldReaction ConditionsOperation in experiment
1: 35% 2: 15% 3: 29% Stage #1: TREHALOSE; tert-butyldimethylsilyl chloride With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: acetic anhydride With pyridine; dmap at 20℃; 6-Tert-butyldimethylsilyl-2,3,4-tri-0-acetyl-a-D-glucopyranosyl 2,3,4,6-tetra-O- acetyl-a-D-glucopyranoside (83); Anhydrous trehalose (3.42 g, 10.0 mmol, 1 eq) was added to 150mL of dry DMF at 50 °C. The solution was cooled down to room temperature and imidazole (1.36g, 20.0 mmol, 2 eq) and TBDMSCl (1.66 g, 11 mmol, 1.1 eq) were added. After 20 minutes, DMF was evaporated under high vacuum to give 8.53 g of yellow oil. This oil was dissolved in pyridine (100 mL) and DMAP (122 mg, 1.0 mmol, 0.1 eq) was added then the mixture was cooled to 0 °C and acetic anhydride (9.27 mL) was added slowly. The solution was stirred overnight at room temperature, upon which time TLC (4: 1 chlorofom/ethyl acetate) revealed the appearance of three new spots (Rf 0.6), (Rf 0.5) and (Rf 0.4) then 100 mL of water was added and the solution extracted with ethyl acetate (3 x 100 mL). The organic layer was dried with MgS04, filtered and evaporated to give 7.46g of a yellow oil. This oil was purified by silica column chromatography (pure chloroform then 9: 1 chloroform/ethyl acetate then 5:5 chloroform/ethyl acetate) to give 1.05g of pure 84 and 5.38g of a mixture of silyl trehalose acetates. This mixture was purified by a second by silica column chromatography (95:5 chloroform/ethyl acetate then 9: 1 chloroform/ethyl acetate then 5:5 chlorofom/ethyl acetate) to give 84 (280 mg, 15% combined yield) followed by 83 (2.63g, 35% yield) and 85 (2.0g , 29% yield)[3); 1H NMR (400 MHz CHLOROFORM- ) δ ppm 0.01 (3 H, s, 1 x CH3), 0.03 (3 H, s, 1 x CH3), 0.86 (9 H, s, 1 x C(CH3)3), 2.03 (3 H, s, 1 x OCOCH3), 2.03 (3 H, s, 1 x OCOCH3), 2.04 (3 H, s, 1 x OCOCH3), 2.05 (3 H, s, 1 x OCOCH3), 2.08(3 H, s, 1 x OCOCH3), 2.09 (3 H, s, 1 x OCOCH3), 2.09 (3 H, s, 1 x OCOCH3), 3.63 (2 H, m, H-6a and H-6b CH2OTBS), 3.93 (1H, ddd, J5A = 10.0 Hz, J5 4.4 Hz, J5_6b = 3.2 Hz, H-5), 4.00 (1 H, dd, J6b-,6a- = 12.0 Hz, J6b-, = 2.0 Hz, H- 6b' OCOCH3), 4.07 (1 H, ddd, J5-A- = 10.0 Hz, J5- - 5.6 Hz, Jyfih- = 2.0 Hz, H-5'), 4.24 (1 H, dd, 12.0 Hz, J6a y = 5.6 Hz, H-6a' CH2OAc), 4.99 (1 H, dd, J2,3 = 10.0 Hz, J2,i = 3.6 Hz, H-2), 5.05 (1 H, dd, J ,y = 10.0 Hz, J4-i3- = 9.6 Hz, H-4'), 5.05 (1 H, dd, J4,5 = 10.0 Hz, J4 = 9.6 Hz, H-4), 5.09 (1 H, dd, Jr, = 10.0 Hz, Jr, = 4.0 Hz, H-2'), 5.25 (1H, d, Ju = 3.6 Hz, H-l), 5.28 (1H, d, Jr,2 < = 4.0 Hz, H-l '), 5.46 (2 H, dd, J3,2 = 10.0 Hz, J3,4 = 9.6 Hz, H-3 and H-3'); 13C NMR (101 MHz CHLOROFORM-;/) δ ppm -5.5, -5.4 (CH3), 18.3 (3 C, 1 x C(CH3)3), 20.6, 20.6, 20.6, 20.6, 20.6, 20.7, 20.8 (7 C, 7x OCOCH3), 25.8 (1 x C(CH3)3), 61.8 (C-6', OCOCH3), 61.9 (C-6 CH2OTBS), 68.1 (C-4'), 68.5 (C-2'), 68.8 (C-4), 69.5 (C-2), 70.1 (C-5'), 70.2 (C-3 '), 70.3 (C-5), 70.6 (C-3), 92.2, 92.3 ( 2x C-1), 169.5, 169.5, 169.5, 169.6, 169.7, 170.1, 170.6 ( 7x C=0); IR (thin film): v = 2955.7, 2854.6, 1754.6 (C=0), 1369.2, 1221.8, 1142.5, 1037.4, 837.7, 780.5 cm"1; MS (ESI+) m/z 768.3 (M+NH4+), 773.2 (M+Na+); HRMS (ESI+) calcd. for C32H5oOi8Si (M+Na+): 773.2659. Found: 773.2651.6-tert-Butyldimethylsilyl-2,3,4-tri-0-acetyl-a-D-glucop y r a n o s y l 6-tert- butyldimethylsilyl 2,3,4-tri-O-acetyl-a-D-glucopyranoside (84)84 was isolated as the upper spot (Rf 0.6) TLC (4: 1 chloroform/ethyl acetate) of the reaction of D-Trehalose with TBDMS-C1. (280 mg, 15%).[aUSD + 157 (c = 1.0 in CHC13); 1H NMR (400 MHz CHLOROFORM-;/) δ ppm 0.02 (6 H, s, 2 x CH3), 0.02 (6 H, s, 2 x CH3), 0.87 (18 H, s, 2 x C(CH3)3), 2.02 (6 H, 2 x OCOCH3), 2.04 (6 H, 2 x OCOCH3), 2.08 (6 H, 2 x OCOCH3), 3.63 (4 H, m, H-6a and H-6b CH2OTBS), 3.93 (2 H, ddd, J5A = 10.0 Hz, J5M 4.4 Hz, JSi6b = 3.2 Hz, H-5), 5.03 (2 H, dd, J2,3 = 10.4 Hz, J2 = 4.0 Hz, H-2), 5.07 (2 H, dd, J4,s = 10.0 Hz, J4 = 9.6 Hz, H-4), 5.25 (2 H, d, Ju = 4.0 Hz, H-l), 5.47 (2 H, dd, J3,2 = 10.4 Hz, J3.4 = 9.6 Hz, H-3); 13C NMR (101 MHz CHLOROFORM- ) δ ppm -5.5 (2 C, 2 x CH3), -5.5 (2 C, 2 x CH3), 18.3(2 C, 2 x C(CH3)3), 20.7, 20.7, 20.8 (6 C, 6 x OCOCH3), 25.9 (2 C, 2 x C(CH3)3), 61.9 (2 C, C-6, C-6'), 68.8 (2 C, C-4 C-4' ), 69.8 (2 C, C-2, C-2'), 70.5 (2 C, C-5,C-5'), 70.6 (2 C, C-3, C-3'), 92.2 ( 2 C, C-1, C-1 '), 169.5, 169.6, 170.2 (6 x C=0); IR (thin film): v = 2955.0, 2857.9, 1755.83 (C=0), 1368.7, 1221.4, 1144.5, 1036.0, 837.1, 780.1, cm"1; MS (ESI+) m/z 840.3 (M+NH4+), 846.3 (M+Na+); HRMS (ESI+) calcd. for C36H62Oi7Si2 (M+Na+): 845.3418, Found: 845.3401.
  • 42
  • [ 99-20-7 ]
  • [ 58479-61-1 ]
  • [ 1253891-15-4 ]
YieldReaction ConditionsOperation in experiment
86% With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.833333h; Inert atmosphere;
86% With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.833333h; Inert atmosphere;
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere; 6-0-tertbutyldiphenylsilyl-2,3,4,2 ',3 ',4, ' 6,-hepta-0-benzyl- a,a -D-trehalose (57); D-trehalose (7.4 g, 21.75 mmol, 1 eq) was dissolved in anhydrous DMF (40 mL). To this was added tert-butyl diphenylchlorosilane (TBDPS-C1) (5 mL, 18 mmol, 0.9 eq) and imidazole (1.4g, 21 mmol, 0.95 eq). Solution was stirred at RT under Ar atmosphere for 18 h. TLC (2: 1 petrol/ethyl acetate) indicated primarily starting material (Rf 0.1) and a small amount of the mono-TBDPS-trehalose. Additional TBDPS-C1 was added (2.5 mL, 9 mmol, 0.45 eq) and reaction was left for a further 18 hours. NaH (8 g, 339 mmol, 15 eq) and benzyl bromide (25 mL, 145 mmol, 7 eq) were added in situ. Reaction was stirred for a further 24 hours under argon, until the desired product could be detected by TLC (5: 1 petrol/ethyl acetate) (Rf 0.85). Column chromatography yielded the desired product as a slightly yellow oil. (4.83 g, 19% over two steps).[ag + 16.13 (c = 0.88 in CHC13); 1H NMR (400 MHz, CHLOROFORM- ) δ ppm 1.14 (9 H, s, 3 x C(CH3)3), 3.47 (1 H, dd, J6a,6b = 10.2 Hz, JSi6b = 1.8 Hz, H-6b'), 3.60 (1 H, dd, J J6a,6b = 10.2 Hz, J5 = 2.7 Hz, H-6a'), 3.64 (1 H, dd, J2,3 = 7.7 Hz, Ju = 4.2 Hz, H-2'), 3.67 (1 H, dd, J2,3 = 7.8 Hz, Ju = 3.8 Hz, H-2), 3.72 (1 H, dd, Jea,6b = 9.7 Hz, J5 = 3.7 Hz, H-6a), 3.78 (1 H, at, J3A = J4,s = 9.4 Hz, H-4'), 3.87 (1 H, dd, J6a,6b = 10.4 Hz, JSi6b = 2.3 Hz, H-6b), 3.97 (1 H, at, J3,4 = J4,s = 9.5 Hz, H-4), 4.13-4.17 (3 H, m, H-5, H-3, H-3') 4.27 (1 H, ddd, J4,5 = 10.0 Hz, J5 = 2.8, JSi6b = 2.7 Hz, H-5'), 4.47 (1 H, d, J = 11.9 Hz, 1 x OCH2Ph), 4.52 (1 H, d, J = 10.6 Hz, 1 x OCH2Ph), 4.57 (1 H, d, J = 12.6 Hz, 1 x OCH2Ph), 4.58 (1 H, d, J = 12.1 Hz, 1 x OCH2Ph), 4.87 (1 H, d, J = 12.1 Hz, 1 x OCH2Ph ), 4.90 (1 H, d, J = 11.1 Hz, 1 x OCH2Ph), 4.94 (1 H, d, J = 9.3 Hz, 1 x OCH2Ph), 4.96 (1 H, d, J = 11.6 Hz, 1 x OCH2Ph), 4.99 (1 H, d, J = 9.6 Hz, 1 x OCH2Ph), 5.01 (1 H, d, J = 9.6 Hz, 1 x OCH2Ph), 5.04 (1 H, d, J = 12.2 Hz, 1 x OCH2Ph), 5.07 (1 H, d, J = 11.0 Hz, 1 x OCH2Ph), 5.09 (1 H, d, J =10.6 Hz, 1 x OCH2Ph), 5.28 (1 H, d, Ju = 3.8 Hz, H-l '), 5.37 (1 H, d, J;,2 = 3.8 Hz, H-l), 7.00 - 7.61 (45 H, m, Ar-H); 13C NMR (101 MHz, CHLOROFORM-^) δ ppm 20.7 (3 x C(CH3)3), 28.1 (1 x C(CH3)3), 62.2 (C-6), 68.2 (C-6'), 70.6 (C-5'), 71.69 (C-5), 72.8 (OCH2Ph), 72.9 (OCH2Ph), 73.6 (OCH2Ph),75.1 (OCH2Ph), 75.3 (OCH2Ph), 75.7 (OCH2Ph), 75.9 (OCH2Ph), 77.70 (C-4 or C- 4'), 77.7 (C-4 or C-4'), 79.5 (C-2'), 80.1 (C-2), 81.9 (C-3 or C-3'), 81.9 (C-3 or C-3'),94.2 (2 C, C-l , C-l '), 126.0, 126.3, 126.4, 127,1 127.2, 127.3, 127.4, 127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.0, 128.1 , 128.2, 128.4, 128.4, 128.5, 128.6, 128.9,129.1, 129.5, 129.7 (7 x OCH2Ph), 138.0, 138.4, 138.5, 138.6, 138.9, 139.0, 139.6 (7 x 1 C, 7 x OCH2Ph); IR (thin film): v = 2925, 2875 (C=CH), 1454, 1444 (C=C), 698 cm"1; MS m/z (ESI+) 1228.6 (M+NH4+); Isotopic distribution: Species observed (M+Na ), peaks observed 1233.53 (100%), 1234.53 (86.6%), 1235.53 (43.1 %), 1236.53 ( 14.5 %), 1237.53 (4.0%), 1238.54 ( 1.1%) peaks calculated 1233.55 (100.0%), 1234.55 (89.7%), 1235.55 (45.2%), 1236.56 (16.0%), 1237.56 (4.2%), 1238.56 (0.6%)
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere;

  • 43
  • [ 99-20-7 ]
  • [ 813-77-4 ]
  • [ 1274878-36-2 ]
YieldReaction ConditionsOperation in experiment
13% With pyridine at 20℃; for 18h; 6-0-(dimethoxyphosphoryl)-D-trehalose (68); To a suspension of D-trehalose (0.25 g, 0.73 mmol, 1 eq) in anhydrous pyridine (10 mL) was added dropwise dimethylchlorophosphate (79 μ, 0.73 mmol, 1 eq). TLC (1 water : 2 isopropanol : 4 ethyl acetate) after 18 hours showed the presence of several products (desired product Rf 0.12). The reaction was quenched with methanol (5 mL). The reaction mixture was concentrated in vacuo, and the residue co-evaporated with toluene to remove pyridine. Silica gel chromatography (1 :2:4, water/isopropanol/ethyl acetate) allowed isolation of the desired product as a white amorphous solid (43 mg, 13%).[a]^8 + 83.3 (c = 1.0 in H20); 1H NMR (500 MHz, DEUTERIUM OXIDE) <5 ppm 3.36 (1 H, at, J3,4 = J4,5 = 9.5 Hz, H-4'), 3.43 (1 H, dd, J3,4 = 10.1 Hz, J4,5 = 9.1 Hz, H-4), 3.56 (1 H, dd, J2,3 = 10.4 Hz, J = 3.8 Hz, H-2'), 3.57 (1 H, t, J2,3 = 10.4 Hz, Ji,2 = 3.8 Hz, H-2), 3.67 (1 H, dd, J6a,6b = 11.5 Hz, J5,6a = 5.0 Hz, H-6a'), 3.72 (1 H, m, H-3'), 3.75 (3 H, d, JP,H = 11.0 Hz, OMe), 3.75-3.81 (3 H, m, H-3, H-5', H- 6b'), 3.76 (3 H, d, JP,H = 11.0 Hz, OMe), 3.91 (1 H, dt, J4,5 = 10.1 Hz, J5,6a = J5,6b = 2.6 Hz, H-5), 4.25-4.29 (2 H, m, H-6a, H-6b), 5.10 (1 H, d, J,2 = 3.8 Hz, H-l '), 5.13 (1 H, d, Ji,2 = 3.8 Hz, H-l); 13C NMR (126 MHz, DEUTERIUM OXIDE) <5 ppm 55.1 (d, JP,c = 8.8 Hz, 2 x OMe), 60.5 (C6'), 66.7 (d, JP,6 = 5.7 Hz, C-6), 69.0 (C-4), 69.6 (C-4'), 70.5 (d, JP,5 6.7 Hz, C-5), 70.9 (C-2), 71.0 (C-2'), 72.2 (C-5'), 72.4 (C-3), 72.5 (C-3'), 93.4 (C-l), 93.5 (C-l '); IR (KBr disc): v = 1260 (P=0), 3486 br (OH) cm"1; MS (ESI+) m/z 451.1 (M+H+), 473.1 (M+Na+), MS (ESI ) m/z 449.6 (M-H+); HRMS (ESI+) calcd. for C14H27O14P (M+Na+): 473.1031, Found: 473.1027.
  • 44
  • [ 99-20-7 ]
  • [ 7493-95-0 ]
  • [ 72441-72-6 ]
  • 45
  • [ 99-20-7 ]
  • [ 67693-22-5 ]
YieldReaction ConditionsOperation in experiment
52% With N-iodo-succinimide; triphenylphosphine
With iodine; triphenylphosphine In N,N-dimethyl-formamide at 80℃; for 2h; Inert atmosphere; 1-O-(2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl)-2,3,4-tri-O-acetyl-6-deoxy-6-iodo-α-Dglucopyranoside (S7) Adapted from the method of Wada et al.8 Anhydrous trehalose (S5) (2.00 g, 5.84 mmol) and triphenylphosphine (4.60 g, 17.5 mmol) were added to a two-necked RBF, dissolved in DMF (20 mL) and the solution was heated at 80°C under an atmosphere of argon. Iodine (3.70 g, 14.6 mmol) was slowly added in portions and heating was continued for a further 2 h, then the mixture was cooled and concentrated to 5 mL in vacuo. Methanol (75 mL) was added and the mixture was stirred at room temperature for 1.5 h. The solvent was evaporated in vacuo and the crude material was dissolved in water (30 mL), extracted with chloroform (3 × 30 mL), and the aqueous layer was then lyophilized. Acetic anhydride (40 mL, 423 mmol) and pyridine (40 mL, 495 mmol) were added to the lyophilized crude 6-deoxy-6-iodo trehalose (S6) and the solution was stirred at room temperature under an atmosphere of nitrogen. After 24 h the solution was poured onto crushed ice (500 mL) and the precipitated product was collected, dissolved in ethyl acetate (150 mL), and washed with aqueous 1 M HCl solution (2 × 150 mL), saturated aqueous sodium bicarbonate solution (2 × 150 mL), and brine (150 mL). The organic layer was dried (MgSO4), filtered, and evaporated in vacuo to afford the crude product which was purified by silica flash column chromatography (ethyl acetate/light petroleum 2:3 v/v) to obtain compound S7, an off-white amorphous solid (0.65 g, 9.8%);
  • 46
  • [ 99-20-7 ]
  • [ 93429-66-4 ]
  • [ 1379657-60-9 ]
YieldReaction ConditionsOperation in experiment
41% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 3h;
41% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 0 - 20℃; for 3h; 1 [000143] Synthesis of 4,6-0-(4-vinylbenzyl)-a-D-glucopyranosyl-(l→l)-a-D-glucopyranoside (2). To a flame dried round bottom flask was dissolved 1 (0.500 g, 2.42 mmol, 1.00 eq) and trehalose (4.15 g, 12.1 mmol, 5.00 eq) in 150 mL DMF, and the resulting mixture was cooled to 0 °C. Next, />-toluene sulfonic acid (92 mg, 0.20 mmol, 0.12 eq) was added and the solution was warmed to 25 °C and stirred for 3 h. Solvent was removed from the resulting crude reaction product in vacuo to give a white solid that was further purified by HPLC (40:60 to 10:90 watenmethanol linear gradient over 30 minutes at lOmL/min). After removal of solvents the resulting product 2 (456 mg, 0.99 mmol, 41% yield) was obtained as a white solid. NMR (600 MHz, D6DMSO) δ: 7.51 (d, 2H, 8.4Hz), 7.46 (d, 2H, 8.4Hz), 6.78 (dd, 1H, 10.8, 17.4Hz), 5.89 (d, 1H, 17.4Hz), 5.59 (s, 1H), 5.32, (d, 1H, 1 1.4Hz), 5.26 (d, 1H, 4.8Hz), 5.03-5.02 (m, 2H), 4.99 (d, 1H, 3.6Hz), 4.92 (d, 1H, 3.6Hz), 4.87-4.85 (m, 2H), 4.45 (dd, 1H, 6, 6Hz), 4.14 (dd, 1H, 4.8, 9.6Hz), 4.04 (ddd, 1H, 4.8, 9.6, 10.2Hz), 3.80 (ddd, 1H, 4.8, 5.4, 9.3Hz), 3.77 (ddd, 1H, 2.1, 4.5, 9.9Hz), 3.69 (dd, 1H, 10.2, 10.2Hz), 3.64-3.60 (m, 2H), 3.53 (ddd, 1H, 5.4, 5.7, 11.7Hz), 3.45-3.40 (m, 2H), 3.32 (ddd, 1H, 3.8, 5.6, 9.4Hz), 3.20 (ddd, 1H, 4.8, 5.4, 9.3Hz). 13C NMR (500 MHz D6DMSO) 8 : 138.4, 138.3, 137.2, 127.6, 126.7, 115.8, 101.6, 101.5, 95.3, 94.8, 82.4, 73.6, 73.1, 72.4, 70.9, 70.5, 69.2, 63.3, 61.6. MS (ESI-MS) calc. for C2iH280, iNa+: 479.15 observed: 479.15, IR: v = 3356, 2921 , 1629, 1455, 1376, 1 148, 1073, 976, 833, 800 cm"1, UV/Vis (H20) λ = 225, 259 nm. The NMR spectra are shown as Figure 1.
  • 47
  • [ 99-20-7 ]
  • [ 67-47-0 ]
YieldReaction ConditionsOperation in experiment
51% With Dowex 50Wx8-200 ion-exchange resin at 100℃; for 3h; Ionic liquid; Sealed tube; General procedure: Dehydrations were performed using sealed tubes in concentrations of 10% (w/w) for both the carbohydrate and the heterogeneous catalyst, using 3 mL of [C4mim]Cl and keeping the temperature at 100 °C with continuous stirring for 3 hrs.
  • 48
  • [ 99-20-7 ]
  • [ 3896-58-0 ]
  • [ 338733-40-7 ]
YieldReaction ConditionsOperation in experiment
81% With novozyme 435 In acetone at 45℃; for 48h; Enzymatic reaction; In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 General procedure: In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 dihydrate (1.8 mmol) in acetone (20 ml) Novozyme 435 (0.28 g) was added, and the mixture was stirred at 45 °C until TLC (ethyl acetate/MeOH/water, 17:4:1) showed completion of the reaction (48-72 h). The mixture was filtered, the solvents were removed, and the residue was subjected to chromatography to afford the diesters. For the mono-acylations the Alcalase from Bacillus licheniformis was used. Selected analytical data: 5 mp: 154-155 °C, [α]D +6.4 (c 0.48, MeOH), MS (ESI, MeOH, LiCl): 877.6 (100%, [M+Li]+, 909.7 (44%, [M+MeOH+Li]+), 1H NMR (500 MHz, DMSO-d6): δ = 5.34-5.26 (m, 4 H, CH∸CH, H-15, H-16), 5.04 (d, J = 5.4 Hz, 2H, H-4), 4.87 (d, J = 4.9 Hz, 2H, H-3), 4.80 (d, J = 3.6 Hz, 2H, H-1), 4.74 (d, J = 6.1 Hz, 2H, H-2), 4.21 (dd, J = 11.6, 1.5 Hz, 2H, H-6A), 4.01 (dd, J = 12.2, 5.3 Hz, 2H, H-6B), 3.90-3.83 (m, 2H, H-5), 3.53 (dd, J = 9.2, 4.9 Hz, 2H, H-3), 3.24 (ddd, J = 9.7, 6.1, 3.7 Hz, 2H, H-2), 3.10 (dd, J = 9.3, 5.5 Hz, 2H, H-4), 2.24 (t, J = 7.4 Hz, H-8), 2.02-1.92 (m, 8H, H-14A,B, H-17A,B), 1.56-1.40 (m, 4H,H-9A,B), 1.32-1.17 (m, 40H, CH2 (H(C-10)-H-(C13), H-(C18)-H-(C23)), 0.83 (t, J = 6.9 Hz, 6H, CH3, H-24) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 172.8 (C-7), 129.73 and 129.70 (C-15, C-16), 93.4 (C-1), 72.85 (C-3), 71.56 (C-2), 70.25 (C-4), 69.82 (C-5), 63.2 (C-6), 33.7 (C-8), 31.4 (C-22), 29.19, 28.93, 28.78, 28.67, 28.57, 28.54 (CH2, C-10-C-13, C-18-C-21), 26.69, 26.67 (C-14, C-17), 24.60 (C-9), 22.2 (C-23), 14.1 (C-24) ppm; analysis for C48H86O13 (871.19): C, 66.18; H, 9.95; found: C, 65.97; H, 7.02.
  • 49
  • [ 99-20-7 ]
  • [ 3896-58-0 ]
  • [ 338733-38-3 ]
YieldReaction ConditionsOperation in experiment
72% With alcalase from Bacillus licheniformis In acetone at 45℃; for 432h; Enzymatic reaction; In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 General procedure: In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 dihydrate (1.8 mmol) in acetone (20 ml) Novozyme 435 (0.28 g) was added, and the mixture was stirred at 45 °C until TLC (ethyl acetate/MeOH/water, 17:4:1) showed completion of the reaction (48-72 h). The mixture was filtered, the solvents were removed, and the residue was subjected to chromatography to afford the diesters. For the mono-acylations the Alcalase from Bacillus licheniformis was used.
  • 50
  • [ 99-20-7 ]
  • [ 1429049-34-2 ]
  • [ 1352549-42-8 ]
YieldReaction ConditionsOperation in experiment
68% With novozyme 435 In acetone at 45℃; for 72h; Enzymatic reaction; In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 General procedure: In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 dihydrate (1.8 mmol) in acetone (20 ml) Novozyme 435 (0.28 g) was added, and the mixture was stirred at 45 °C until TLC (ethyl acetate/MeOH/water, 17:4:1) showed completion of the reaction (48-72 h). The mixture was filtered, the solvents were removed, and the residue was subjected to chromatography to afford the diesters. For the mono-acylations the Alcalase from Bacillus licheniformis was used.
  • 51
  • [ 99-20-7 ]
  • [ 1429049-34-2 ]
  • [ 1429049-33-1 ]
YieldReaction ConditionsOperation in experiment
74% With alcalase from Bacillus licheniformis In acetone at 45℃; for 432h; Enzymatic reaction; In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 General procedure: In a typical experiment, to a solution of the vinyl carboxylate (5.3 mmol) and 1 dihydrate (1.8 mmol) in acetone (20 ml) Novozyme 435 (0.28 g) was added, and the mixture was stirred at 45 °C until TLC (ethyl acetate/MeOH/water, 17:4:1) showed completion of the reaction (48-72 h). The mixture was filtered, the solvents were removed, and the residue was subjected to chromatography to afford the diesters. For the mono-acylations the Alcalase from Bacillus licheniformis was used.
  • 52
  • 3,3'-diethoxypropyl methacrylate [ No CAS ]
  • [ 99-20-7 ]
  • [ 1446418-67-2 ]
YieldReaction ConditionsOperation in experiment
37% With toluene-4-sulfonic acid; hydroquinone at 100℃; for 3h; 6 [000190] Synthesis of 15 [000190] Synthesis of 15. Trehalose (3.96 g, 1.16>< 10"2 mol) was dissolved in 100 °C DMF (72 mL). -TsOH (44 mg, 2.31 x 10"' mmol) and hydroquinone (12.73 mg, 1.16x 10"' mmol) were added into the solution. After stirring for 5 min, 14 (500 mg, 2.31 mmol) was added to the reaction slowly. After 3 h, the reaction was stopped and the solvent was removed in vacuo. The crude product was purified by HPLC (50 % MeOH in H20) and lyophilized resulting white powder (403.6 mg) with 37 % yield. NMR (500 MHz in D6DMSO) δ: 6.04 (s, 1H), 5.68-5.67 (t, J = 1.59 Hz, 1H), 5.10-5.09 (d, J = 5.31 Hz, 1H), 4.93-4.89 (m, 3H), 4.83-4.82 (d, J = 3.50 Hz, 1H), 4.78-4.76 (m , 2H), 4.70-4.68 (t, J = 5.00 Hz, 1H), 4.36-4.33 (t, J = 5.95 Hz, 1H), 4.16-4.13 (m, 2H), 3.97-3.94 (m, 1H), 3.89-3.84 (m, 1H), 3.69-3.64 (m, 2H), 3.57-3.53 (m, 2H), 3.49-3.41 (m, 2H), 3.35 (1H), 3.26-3.22 (m, 1H), 3.17-3.12 (m, 2H), 2.01-1.88 (m, 5H). 13C NMR (500 MHz in D6DMSO) δ: 166.9, 136.1, 126.2, 99.2, 94.5, 94.1, 81.4, 73.0, 73.0, 72.4, 71.8, 70.3, 69.8, 68.1, 62.7, 61.0, 60.6, 33.5, 18.3. IR: v = 3365, 2934, 1713, 1636, 1305, 1 148, 979 cm"1. ESI-MS (± 1.0) observed (predicted): Na+ 489.1577 (489.1584).
  • 53
  • [ 99-20-7 ]
  • [ 1592-20-7 ]
  • [ 1446418-69-4 ]
YieldReaction ConditionsOperation in experiment
20% With sodium hydroxide In dimethyl sulfoxide at 25℃; for 24h; 6 [000192] Synthesis of 16. [000192] Synthesis of 16. 16 was synthesized by modifying a literature procedure where the trehalose was substituted on multiple hydroxyl groups (Teramoto and Shibata, 2004). NaOH (4.44 g, 1.14 x lO"1 mol) was added to DMSO (96 mL) and stirred for 5 min. Trehalose (4.86 g, 2 1.42x l0" mol) was then added to the reaction flask. After all the trehalose dissolved, 4-vinyl benzyl chloride (0.4 mL, 2.84x 10"3) was slowly added and reaction solution changed to bright yellow. The reaction was stirred for 24 h at 25 °C and precipitated into 4 L of DCM under ice bath. Precipitates were dried in vacuo and purified by HPLC (50 % MeOH in H20). After lyophilization the desired monosubstituted product (261.1 mg) was obtained as white powder with 20 % yield. NMR (500 MHz in D20) δ: 7.47-7.45 (m, 2H), 7.35-7.33 (m, 2H), 6.77-6.71 (m, 1H), 5.84-5.80 (d, J = 17.69 Hz, 1H), 5.30-5.28 (d, J = 1 1.42 Hz, 1H), 5.23-5.22 (d, J = 3.68 Hz, 1H), 5.14-5.13 (d, J = 4.05 Hz, 1H), 4.69-4.61 (m, 2H), 3.91-3.51 (m, 10H), 3.45-3.39 (m, 2H). 13C NMR (500 MHz in D20) δ: 137.5, 136.6, 136.2, 128.9, 126.4, 114.7, 93.5, 91.4, 78.7, 73.2, 72.4, 72.2, 72.0, 72.0, 71.0, 69.8, 69.2, 60.6, 60.1. IR: v = 3369, 2931 , 1642, 1408, 1368, 1 147, 1083, 1044, 989 cm"1. ESI-MS (± 1.0) observed (predicted): Na+ 481.1692 (481.1686).
  • 54
  • [ 99-20-7 ]
  • [ 76-83-5 ]
  • [ 76054-83-6 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 90℃; for 24h; Inert atmosphere; 6 [000194] Synthesis of 17. 17 was synthesized modifying a previous literature where the trehalose was substituted with a trityl group on multiple hydroxyl groups (Kurita, Masuda, et al., 1994). Trehalose (4.91 g, 14.35 mmol, 1.5 eq) was stirred in 20 mL pyridine for 30 min. Trityl chloride (TrCl, 2.67 g, 9.57 mmol, 1.0 eq) was then added, and the reaction mixture was stirred under Ar at 90°C for 24h. After cooling to room temperature, acetic anhydride (12 mL, 127.2 mmol, 13.3 eq) was added, and the reaction mixture was stirred under Ar at 23 °C for 21 h. Pyridine was removed under high vacuum. To the crude solid, H20 was added and extracted with CHC13, the organic layer was then sequentially washed with 0.1 N HC1, H20, sat. NaHC03, and brine. The organic layer was then dried with MgS04 and concentrated under reduced pressure. The crude was purified through silica gel flash chromatography with EtOAc/Hexane=3/4 + 1% NEt3 (Rp-0.3) to obtain 2.62 g white solid with 31 % yield. NMR (500 MHz in CDC13) δ: 7.38-7.21 (m, 15H), 5.50-5.45 (m, 2H), 5.40-5.37 (dd, J= 3.85, 7.85 Hz, 2H), 5.18-5.15 (dd, J= 3.85, 10.2 Hz, 2H), 5.13-5.06 (m, 2H), 4.27-4.23 (m, IH), 4.14-4.04 (m, 3H), 3.10-3.03 (m, 2H), 2.1 1-1.74 (s, 21H). 13C NMR (500 MHz in CDC13) δ: 170.81, 170.25, 170.12, 169.91, 169.72, 169.69, 169.30, 143.47, 128.71, 128.01 , 127.24, 92.51, 92.48. 86.71 , 70.43, 70.38, 70.27, 69.85, 69.61 , 68.99, 68.67, 68.35, 61.94, 61.81 , 20.88, 20.81, 20.79, 20.77, 20.67, 20.54. IR: v = 2956, 2941, 1746, 1449, 1367, 1239, 1213, 1072, 1030, 985, 962, 902, 805, 766, 749. ESI-MS (± 1.0) observed (predicted): Na+ 901.2892 (901.2895).
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide
  • 55
  • [ 99-20-7 ]
  • [ 2186-92-7 ]
  • [ 1456898-37-5 ]
YieldReaction ConditionsOperation in experiment
97% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere;
96% With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 60℃; for 5h; Inert atmosphere;
  • 56
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 67398-72-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With pyridine; trityl chloride In toluene at 90℃; for 16h; Stage #2: acetic anhydride In toluene at 20℃; for 16h; Stage #3: With iron(III) chloride In dichloromethane at 20℃; for 1h; 4 EXAMPLE 4 Compounds 16-24 can be prepared as follows: Anhydrous α,α-D-trehalose (1 eq) is coevaporated from toluene and dried overnight in vacuo. Trityl chloride (4 eq) and anhydrous pyridine (4 mL) are added to the trehalose. The solution is heated to 90° C. and stirred for 16 hours. After 16 hours, the appropriate anhydride (10 eq) is added to the reaction solution. The reaction solution is allowed to stir at room temperature for 16 hours. Then the solvent is evaporated in vacuo, and the residue is purified by silica gel chromatography. The resulting purified compound is then dissolved in methylene chloride (3 mL), and iron (III) chloride (2.6 eq) is added to the solution. The reaction is stirred for 1 hour at room temperature, after which water (3 mL) is added to the flask. The solution is stirred for 20 minutes, and then the organic phase is extracted with methylene chloride (2×10 mL) and subsequently washed with saturated NaCl (1×10 mL). The organic phase is dried with anhydrous sodium sulfate, and filtered. The solvent is evaporated in vacuo and then is purified by silica gel chromatography.
  • 57
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • 2,2',3,3'-tetra-O-acetyl-α,α-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% Stage #1: TREHALOSE With p-Anisaldehyde dimethyl acetal; camphor-10-sulfonic acid In N,N-dimethyl-formamide Inert atmosphere; Stage #2: acetic anhydride With pyridine In N,N-dimethyl-formamide Inert atmosphere; Stage #3: With acetic acid In water; N,N-dimethyl-formamide Inert atmosphere;
Stage #1: TREHALOSE With benzaldehyde dimethyl acetal; toluene-4-sulfonic acid In N,N-dimethyl-formamide; toluene at 100℃; Stage #2: acetic anhydride With pyridine In acetonitrile for 16h; 5 EXAMPLE 5 Compounds 25-33 can be prepared as follows: Anhydrous α,α-D-trehalose (1 eq) and paratoluesulfonic acid (p-TSA) (0.05 eq) are separately coevaporated with toluene and dried overnight in vacuo. Anhydrous DMF (2.5 mL) is added to the dried, anhydrous α,α-D-trehalose. Another portion of anhydrous DMF (2.5 mL) is added to a stirred suspension of p-TSA and (dimethoxymethyl)benzene (1 eq). The solution of p-TSA and (dimethoxymethyl)benzene in DMF is then added to the solution of anhydrous trehalose in DMF, and the entire reaction solution is stirred and heated at 100° C. for 10 minutes. The reaction is concentrated in vacuo for 3 minutes under pressure. The reaction flask is then flushed with N2, and another portion of (dimethoxymethyl)benzene (1 eq) is added to the reaction. The heating procedure is repeated, and the reaction is again concentrated in vacuo for 3 minutes. The reaction flask is then flushed with N2, and more (dimethoxymethyl)benzene (0.25 eq) is added to the reaction. After stirring at room temperature for 10 minutes, the reaction is evaporated in vacuo, and the residue is purified by silica gel chromatography. The resulting purified compound is dissolved in a mixture of acetonitrile (3 mL) and pyridine (3 mL). The appropriate anhydride (5.2 eq) is added to the reaction solution, and the reaction is allowed to stir for 16 hours. The solvent is then evaporated in vacuo, and the residue is purified by silica gel chromatography. The resulting purified compound is then dissolved in acetic acid (1.14 mL), and the solution is heated to 95° C. Water (760 μL) is then added to the stirred suspension drop-wise, and the reaction is stirred for 30 minutes at 95° C. Toluene (2×5 mL) is added to the reaction solution, and the solution is concentrated in vacuo, and the residue is purified using silica gel chromatography.
  • 58
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 68643-14-1 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With chloro-trimethyl-silane; triethylamine In dichloromethane at 0 - 20℃; for 16h; Stage #2: With potassium carbonate In methanol; dichloromethane at 0 - 20℃; for 1h; Stage #3: acetic anhydride Further stages; 6 EXAMPLE 6 Compounds 34-42 can be prepared as follows: Triethylamine (40 eq) is added to a stirred suspension of anhydrous α,α-D-trehalose (1 eq) in anhydrous CH2Cl2 (3 mL), and the suspension is cooled to 0° C. Trimethylsilyl chloride (12 eq) is then added drop-wise to the solution, and the reaction is stirred for 12 hours. After 12 hours, the solution is cooled to 0° C., and another portion of trimethylsilyl chloride (4 eq) is added to the solution. The reaction is allowed to stir for 4 hours at room temperature, after which the organic layer is extracted with CH2Cl2 (3×20 mL), dried with anhydrous sodium sulfate, filtered, and the solvent is evaporated to afford a cream colored solid. This solid is dissolved in methanol (5.4 mL) and CH2Cl2 (1.8 mL), and the solution is cooled to 0° C. Potassium carbonate (0.12 eq) is then added to the solution. The reaction is allowed to stir while warming to room temperature for 1 hour. After 1 hour, glacial acetic acid is added drop-wise to the reaction solution until the pH of the solution drops to 7. The solvent is evaporated in vacuo, and the residue is purified by silica gel chromatography. The resulting purified compound is dissolved in pyridine (3 mL) and the appropriate anhydride (2.6 eq) is added to the solution. A catalytic amount of DMAP (0.05 eq) is added to the reaction, and the reaction is stirred for 16 hours at room temperature. The solvent is evaporated in vacuo, and the residue is purified by silica gel chromatography. The resulting purified compound is dissolved in methanol (6 mL) and CH2Cl2 (1 mL). Dry Dowex 50WX8-200 resin (283 mg) is added to this solution, and the reaction is stirred for 15 minutes at room temperature. The reaction solution is filtered, and the solvent is evaporated in vacuo. The resulting residue is purified by silica gel chromatography.
  • 59
  • 6-O-(4-hydroxy-3-methoxybenzoyl)-α,α-trehalose [ No CAS ]
  • [ 99-20-7 ]
YieldReaction ConditionsOperation in experiment
With water; potassium hydroxide In methanol at 20℃; for 2h; Hydrolysis of compound 1 and 2 Compound 1 (0.5mg) was dissolved in 3% KOH-MeOH (1ml) and kept at room temperature for 2h. The mixture was neutralized with 1M HCl. Compound 2 (1mg) in 2M HCl (0.2mL) was refluxed at 70°C for 3h. Reaction mixtures were separately subjected to silica gel TLC, together with the standard samples, using CHCl3-MeOH-H2O (6:4:1, v/v/v) and n-BuOH-AcOEt-H2O (5:1:4, v/v/v, upper phase) as the developing solvents and using 10% aqueous H2SO4 as the detection reagent. α,α-Trehalose was detected from the compound 1 and glucose, xylose and rhamnose were detected from the compound 2.
  • 60
  • [ 99-20-7 ]
  • [ 4074-90-2 ]
  • trehalose divinyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With lipase B from Candida antarctica In acetone at 50℃; for 48h; Enzymatic reaction; 2 To synthesize a multiffinctional thiol trehalose a two step reaction scheme involving a divinyl ester intermediate was applied. The first step of the synthesis involved reacting trehalose dihydrate with a twelve mole excess of a divinyl ester crosslinker such as divinyl adipate or divinyl sebacate in the presence of Novozyme 435 (Lipase B from Candida antarctica that is attached to acrylic resin) in acetone at 50° C. under agitated conditions for 48 hours. The reaction mixture was filtered to remove the lipase resin and then purified by precipitating three times in cold hexane. The purified trehalose divinyl ester was collected by filtration. The synthesis of this divinyl ester trehalose has been reported previously as a monomer for making linear ployesters. See Park, O.-J.; Kim, D.-Y.; Dordick, J. S. Enzyme-catalyzed synthesis of sugar- containing monomers and linear polymers. Biotechnol. Bioeng. 2000, 70, 208-216, which is incorporated herein by reference as if fully set forth. To synthesize the multifunctionalized thiol trehalose, the purified trehalose divinyl ester was reacted with a thiol containing primary alcohol. The thiol containing primary alcohol could include one or more of 2,3 -dimercapto- 1 -propanol, 2-mercaptoethanol, or1 -thioglycerol. As an example, a 4 mole excess of 2,3-dimer- capto-1 -propanol was allowed to react with trehalose divinyl ester in the presence of Novozyme 435 (Lipase B from Candida antarctica that is attached to acrylic resin) in acetone at 50° C. for 24 hours under inert conditions. Afier 24 hours the reaction was stopped by filtering off the Lipase B resin and the tetra functionalized thiol containing trehalose is purified by precipitating three times in ethyl ethet Purified tetra functionalized thiol trehalose was collected by filtering off the ethyl ether after the final precipitation step. Product was characterized using LC-MS (FIG. 5) and 1H-NMR (FIG. 6). See Reaction Scheme 4, below.
  • 61
  • [ 28752-82-1 ]
  • [ 99-20-7 ]
  • 4,6,4',6'-di-O-(2-allyloxybenzylidene)-α,α-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With Amberlyst 15 In N,N-dimethyl-formamide; benzene for 48h; Reflux; 2.2. Synthesis of 4,6,4',6'-di-O-(x-allyloxybenzylidene)-α,α-D-trehalose(2-; 3- or 4-AllTD) General procedure: Trehalose acetals were synthesized based on a method previouslydescribed for the synthesis of 4,6,4',6'-di-O-(4-allyloxybenzylidene)-α,α-D-trehalose with some modifications[40]. The acetalization reaction was carried out using a two-neckround-bottom flask equipped with a DeaneStark trap, thermometerand reflux condenser. 30 mL of anhydrous benzene, 3.2 mL of2-, 3- or 4-allyloxybenzaldehyde and 1.13 g of Amberlyst 15 wereadded to a solution of 2.7 g (7.9 mmol) of dried trehalose in 15 mL of anhydrous DMF. The reaction was carried under reflux for 48 h.After this time, the catalyst was filtered off and benzene wasremoved under reduced pressure. A solution of the product in N,N-dimethylformamide(DMF) was treated several times with aqueous NaHCO3 and deionized water. The precipitate was washed threetimes with diethyl ether (30 mL) in order to remove x-allyloxybenzaldehyde.White powder was dried under a vacuum for 24 h.
  • 62
  • [ 99-20-7 ]
  • [ 40359-32-8 ]
  • 4,6,4',6'-di-O-(3-allyloxybenzylidene)-α,α-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With Amberlyst 15; In N,N-dimethyl-formamide; benzene; for 48h;Reflux; General procedure: Trehalose acetals were synthesized based on a method previouslydescribed for the synthesis of 4,6,4',6'-di-O-(4-allyloxybenzylidene)-alpha,alpha-D-trehalose with some modifications[40]. The acetalization reaction was carried out using a two-neckround-bottom flask equipped with a DeaneStark trap, thermometerand reflux condenser. 30 mL of anhydrous benzene, 3.2 mL of2-, 3- or 4-allyloxybenzaldehyde and 1.13 g of Amberlyst 15 wereadded to a solution of 2.7 g (7.9 mmol) of dried trehalose in 15 mL of anhydrous DMF. The reaction was carried under reflux for 48 h.After this time, the catalyst was filtered off and benzene wasremoved under reduced pressure. A solution of the product in N,N-dimethylformamide(DMF) was treated several times with aqueous NaHCO3 and deionized water. The precipitate was washed threetimes with diethyl ether (30 mL) in order to remove x-allyloxybenzaldehyde.White powder was dried under a vacuum for 24 h.
  • 63
  • [ 99-20-7 ]
  • [ 40663-68-1 ]
  • 4,6,4',6'-di-O-(4-allyloxybenzylidene)-α,α-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With Amberlyst 15 In N,N-dimethyl-formamide; benzene for 48h; Reflux; 2.2. Synthesis of 4,6,4',6'-di-O-(x-allyloxybenzylidene)-α,α-D-trehalose(2-; 3- or 4-AllTD) General procedure: Trehalose acetals were synthesized based on a method previouslydescribed for the synthesis of 4,6,4',6'-di-O-(4-allyloxybenzylidene)-α,α-D-trehalose with some modifications[40]. The acetalization reaction was carried out using a two-neckround-bottom flask equipped with a DeaneStark trap, thermometerand reflux condenser. 30 mL of anhydrous benzene, 3.2 mL of2-, 3- or 4-allyloxybenzaldehyde and 1.13 g of Amberlyst 15 wereadded to a solution of 2.7 g (7.9 mmol) of dried trehalose in 15 mL of anhydrous DMF. The reaction was carried under reflux for 48 h.After this time, the catalyst was filtered off and benzene wasremoved under reduced pressure. A solution of the product in N,N-dimethylformamide(DMF) was treated several times with aqueous NaHCO3 and deionized water. The precipitate was washed threetimes with diethyl ether (30 mL) in order to remove x-allyloxybenzaldehyde.White powder was dried under a vacuum for 24 h.
  • 64
  • [ 99-20-7 ]
  • [ 93429-66-4 ]
  • C30H34O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: TREHALOSE With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 0.166667h; Stage #2: 4-vinylbenzaldehyde diethyl acetal In N,N-dimethyl-formamide at 100℃; for 2h; 2; 3 Synthesis of Bis-Styrenyl Acetal Trehalose Crosslinker (bis-SAT). To the flame- dried reaction flask, trehalose (398 mg, 1.16 mmol) and DMF (4 mL) were added. /?-TsOH (7.08 mg, 3.72* 10~2 mmol) was added and the reaction was stirred for 10 min immersed in a 100 °C oil bath. To the reaction 4-vinylbenzaldehyde diethyl acetal (600 mg, 2.91 mmol) was slowly added and the reaction was stirred at 100 °C for 2 h. After the reaction was complete, 80% of DMF was removed in vacuo and the remaining solution precipitated in benzene. The precipitate was filtered with saturated NaHC03 and washed with H20 extensively. The filter cake was collected and recrystallized in EtOH : H20 = 2 : 1 resulting in 478.5 mg white powder with 72% yield. 1H NMR (500 MHz in D6DMSO) δ: 7.48-7.44 (m, 8H), 6.80-6.74 (m, 2H), 5.84-5.81 (d, J = 18.15 Hz, 2H), 5.56 (s, 2H), 5.29-5.27 (d, J = 10.37 Hz, 2H), 5.10-5.09 (m, 2H), 4.19-4.16 (m, 2H), 4.00-3.97 (m, 2H), 3.93-3.89 (m, 2H), 3.72-3.68 (t, J = 10.81 Hz, 2H), 3.58-3.53 (m, 2H), 3.47-3.44 (m, 4H), 3.32-3.30 (m, 2H). ESI-MS (± 1.0) observed (predicted): H+ 571.22 (571.22).
  • 65
  • [ 99-20-7 ]
  • [ 1592-20-7 ]
  • [ 1446418-69-4 ]
  • C30H38O11 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In dimethyl sulfoxide at 25℃; for 24h; 3; 6 One pot reaction for synthesis of trehalose monomers and cross-linkers(Crude SET). The one pot reaction for the monomers and cross-linkers was performed by modifying a previously reported literature procedure (Teramoto and Shibata, 2004). Sodium hydroxide (NaOH, 4.44 g, l .l l l0_1 mol) was added to dimethyl sulfoxide (DMSO, 96 mL). After stirring for 5 min, trehalose (4.86 g, 1.42x l0"2 mol) was added to the reaction. After all the trehalose was dissolved, 4-vinylbenzyl chloride (0.4 mL, 2.84* 10~3 mol) was slowly added to the reaction and was stirred for 24 h at 25 °C. The crude product was then precipitated into 2 L of DCM to remove highly modified trehalose. The resulting solid was dried in vacuo and used for gelation without further purification.
  • 66
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 76-83-5 ]
  • [ 113842-78-7 ]
YieldReaction ConditionsOperation in experiment
39% Stage #1: TREHALOSE; trityl chloride With pyridine at 50℃; for 48h; Stage #2: acetic anhydride at 21℃; 1 Synthesis of thiolated trehalose monomeric unit A thiol-functionalized trehalose molecule was synthesized in 5 steps, with 19 % overall yield (Scheme 1; the numericals of compounds are limited in Example 1). Briefly, the primary alcohols of trehalose was selectively functionalized using the bulky trityl protecting group and the remaining hydroxyls converted to the acetate ester using acetic anhydride to form 2. Deprotection of the trityl ether under acidic conditions, followed by tosylation of the exposed alcohol led to tosyl ester 4, which was displaced using the nucleophile potassium thioacetate to yield the thioacetate ester 5. Selective removal of the more labile thioester led to the thiolated trehalose 6.
19% Stage #1: TREHALOSE With pyridine at 90℃; for 2.5h; Inert atmosphere; Stage #2: trityl chloride at 90℃; for 19h; Inert atmosphere; Stage #3: acetic anhydride at 20℃; for 24h;
  • 67
  • [ 99-20-7 ]
  • [ 100-39-0 ]
  • [ 136090-72-7 ]
  • [ 103128-34-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With benzaldehyde dimethyl acetal; toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; for 5.66667h; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran; paraffin oil at 20℃; for 45h; Cooling with ice; Stage #3: With triethylsilane; trifluoroacetic acid In dichloromethane at 0℃; for 3h; 1.1; 1.2; 1.3 Synthesis of Lentztrehalose A Via Compound Represented by Structural Formula 4a 1) Trehalose (2.33 g, 6.80 mmol), benzaldehyde dimethylacetal (1.02 mE, 1 equivalent), and p-TsOH (59 mg, 5 mol %) were dissolved in DMF (30 mE) and then heated to 1000 C. Twenty minutes later, the reaction system was reduced in pressure to 160 mmHg and stirred for 20 mm. Henzaldehyde dimethylacetal (1.02 mE, 1.0 equivalent) was added thereto, and then stirred under reduced pressure of 160 mmHg and the same condition for 1 hour. Further, benzaldehyde dimethylacetal (0.25 mE, 0.25 equivalents) was added thereto, and continued to stir under reduced pressure of 160 mmHg for 4 hours. The reaction system was cooled to room temperature, concentrated under reduced pressure, and then neutralized with triethylamine. The resultant crude product was used in the next reaction without further purification.j0144] 2) The whole quantity of the crude product was dissolved in tetrahydroffiran (70 mE), followed by adding sodium hydride (dispersed in 60% liquid paraffin (the same applied to sodium hydride described below)) (2.72 g, 10 equivalents), THAI (176 mg, 7 mol %), and benzyl bromide (4.85 mE, 6 equivalents) thereto sequentially under ice cooling and then stirring at room temperature for 45 hours. The resultant reaction liquid was poured into ice-water (40 mE) and quenched, from which an organic layer was separated. An aqueous layer was extracted with ether (30 mEx3). The combined organic layer was washed with aqueous hydrochloric acid solution (1 N, 20 mE) and saturated aqueous sodium bicarbonate solution (40 mE), and then dried over sodium sulfate. The solvent was distilled off, followed by purifying by silica gel colunm chromatography (hexane:ethyl acetate=6: 1) to thereby obtain a benzyl protected product (4.89 g). The benzyl protected product was dissolved in methylene chloride (300 mE), followed by adding at 0° C. triethylsilane (11.7 mE, 15 equivalents) and trifluoroacetic acid (5.61 mE, 15 equivalents) thereto and then stirring at the same temperature for 3 hours. Saturated aqueous NaHCO3 solution (100 mE) was added thereto, and then stirred for 5 mm. Then, an organic layer was separated and washed with saturated aqueous sodium chloride solution. An aqueous layer was extracted with methylene chloride (100 mE). The resultant organic layer was washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. Then, the solvent was distilled off. The resultant crude syrup was purified by silica gel column chromatography (hexane:ethyl acetate=4: 1 to 3:1) to thereby obtain a compound represented by Structural Formula 4a (3.11 g, 3.52 mmol, 52% in 3 steps) as white powder and a compound represented by Structural Formula 4a’ (337 mg, 0.346 mmol, 5% in 3 steps) as colorless syrup. -Compound Represented by Structural Formula 4a- j0146] Results of a melting point, a specific rotation, a ‘H NMR spectrum, a ‘3C NMR spectrum, and a HRMS (ESI) analysis of the compound represented by Structural Formula 4a are as follows.10147] Melting point: 101° C. to 103° C. (dec.). j0148] Specific rotation: [a]25D=79 (c=1.3, CHC13). j0149] ‘H NMR (400 MHz, CDC13): ö 7.38-7.33 (m, 8H), 7.30-7.23 (m, 22H), 5.23 (d, J=3M Hz, 2H), 5.00 (d, J=11.4 Hz, 2H), 4.79 (d, J=11.4 Hz, 2H), 4.69 (d, J=12.1 Hz, 2H), 4.63 (d, J=12.1 Hz, 2H), 4.50 (d, J=12.1 Hz, 2H), 4.44 (d, J=12.1 Hz, 2H), 4.13-4.10 (m, 2H), 3.87 (t, J=9.6 Hz, 2H), 3.59 (t, J=9.6 Hz, 2H), 3.56 (dd, J=9.6 Hz, J=3.6 Hz, 2H),3.53-3.45 (m, 4H), 2.38 (bs, 2H).j0150] ‘3C NMR (100 MHz, CDC13): ö 138.9, 138.1, 138.0, 128.7, 128.5, 128.5, 128.1, 127.9, 127.8, 127.8,127.6, 94.3, 81.1, 79.0, 75.4, 73.7, 72.5, 70.8, 70.7, 69.3. j0151] HRMS (ESI) analysis: calcd. for C54H580,,K mlz921.3611 [M+K], found 921.3598. -Compound Represented by Structural Formula 4a’- 10152] Results of a specific rotation, a ‘H NMR spectrum, a ‘3C NMR spectrum, and a HRMS (ESI) analysis of the compound represented by Structural Formula 4a’ are as follows.10153] Specific rotation: [a]25D=88 (c=1.0, CHC13). j0154] ‘H NMR (400 MHz, CDC13): ö 7.37-7.20 (m, 33H), 7.13-7.11 (m, 2H), 5.24 (d, J=3.4 Hz, 1H), 5.23 (d, J=3.4 Hz, 1H), 5.00 (d, J=11.4 Hz, 1H), 4.99 (d, J=11.0 Hz, 1H), 4.86 (d, J=11.0 Hz, 1H), 4.81 (d, J=10.5 Hz, 1H), 4.79 (d, J=11.4 Hz, 1H), 4.71-4.64 (m, 4H), 4.54 (d, J=12.4 Hz, 1H), 4.50 (d, J=12.4 Hz, 1H), 4.45 (d, J=10.5 Hz, 1H), 4.43 (d, J=12.4 Hz, 1H), 4.37 (d, J=12.4 Hz, 1H), 4.17-4.11 (m, 2H), 4.03 (t, J=9.4 Hz, 1H), 3.87 (t, J=9.4 Hz, 1H), 3.68 (t, J=9.6 Hz, 2H), 3.59 (dd, J=9.6 Hz, J=3.2 Hz, 1H), 3.56 (dd,J=9.8 Hz, J=3.4 Hz, 1H), 3.53-3.44 (m, 3H), 3.36 (d, J=10.1 Hz, 1H), 2.38 (d, J=2.3 Hz, 1H).10155] ‘3C NMR (100 MHz, CDC13): ö 138.9, 138.9,138.4, 138.2, 138.1, 138.0, 137.9, 128.6, 128.5, 128.4,128.1, 128.0, 128.0, 127.8, 127.8, 127.8, 127.7, 127,7,127.6, 127.6, 127.4, 94.5, 94.4, 81.9, 81.1, 79.4, 79.1, 77.7,75.7,75.4, 75.2, 73.7,73.6, 72.8, 72.5, 70.9, 70.7, 70.6, 69.2,68.2.10156] HRMS (ESI) analysis: calcd. for C64H640,,K mlz1101.4080 [M+K], found 1101.4067.
  • 68
  • [ 99-20-7 ]
  • [ 4205-23-6 ]
YieldReaction ConditionsOperation in experiment
With trehalase 1 from Saccharomyces cerevisiae In glycerol at 30℃; Enzymatic reaction; Enzyme Activity Measurements. The trehalase activity of Nth1 and its mutantswere measured by estimating the glucose produced by the hydrolysis oftrehalose, using a stopped assay, as described earlier (23, 49). The assay wasperformed at 30 °C in buffer 3 [20 mM Tris·HCl, 150 mM NaCl, 10 mM CaCl2(where needed), 10% (wt/vol) glycerol at pH 7.5] and 30 mM trehalose. Thefinal concentrations of Nth1 and Bmh1 (where needed) were 100 nM and15 μM, respectively. The specific trehalase activity of Nth1 was determined asmicromol glucose liberated/min/mg protein.
  • 69
  • [ 99-20-7 ]
  • [ 97-72-3 ]
  • trehalose octaisobutyrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With pyridine; dmap at 20 - 48℃; Inert atmosphere; 2 General experimental procedure for synthesis of carbohydrate esters General procedure: Carbohydrates (di- and trisaccharides, typically 10-100 g) were suspended in dry pyridine under inert atmosphere (N2). Hereafter, acetic, propionic or isobutyric anhydride (2.2 eq. pr. hydroxyl group) was carefully added. Then, a catalytic amount of DMAP (0.1 eq.) was added. The reactions were heated to 48°C overnight and then continued for -24 hours at room temperature until TLC and MALDI-TOF showed complete acylation of the starting material. The reactions were concentrated under reduced pressure and co-evaporated with toluene. The concentrates were dissolved in CHC and washed with NaHCO3 (aq.) (3x), brine (1 x) and water (2x). The organic phases were dried with MgSO4 (s), filtered, concentrated under reduced pressure and dried in vacuo. Yields and reported spectra of individual sugar esters can be found below. Raffinose undecaisobutyrate
  • 70
  • [ 99-20-7 ]
  • C12H16O13(2-)*2Na(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate In water; acetonitrile at 0 - 20℃; for 6h; regioselective reaction; General procedure for TEMPO-mediated oxidation using NaOCl: General procedure: TEMPO (0.2 equiv per 1o-OH group) was added to a stirred solution of sugar/nucleoside (0.1 - 0.5 mmol), NaHCO3 (2 equiv per 1o-OH group) and NaOCl (3 equiv per 1o-OH group, 8.25% aqueous solution) in a MeCN (1 mL) (H2O came from aqueous solution of NaOCl) at 0 oC; stirring was continued at the same temperature for 5 min. After that the resulting mixture was warmed to room temperature and stirred for 15 min to complete one cooling-warming cycle. Again, the temperature of the reaction mixture was lowered to 0 oC for 5 minutes and then warmed to room temperature for 15 minutes to complete the second warming-cooling cycle and so on until most of the starting material was consumed (by mass/TLC analysis). After completion the reaction mixture was diluted with H2O and washed with EtOAc (to remove TEMPO). Aqueous layer was concentrated under vacuum to afford the crude product which was further purified by silica gel flash chromatography/ion exchange resin to afford the pure acid product as sodium salt/triethyl ammonium salt.
  • 71
  • [ 99-20-7 ]
  • [ 180206-32-0 ]
  • α,α-D-trehalose octakis(2,3,4-trihydroxybenzoate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: TREHALOSE; 2,3,4-tris(benzyloxy)benzoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane Inert atmosphere; Reflux; Stage #2: With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol at 30℃;
54% Stage #1: TREHALOSE; 2,3,4-tris(benzyloxy)benzoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane Reflux; Inert atmosphere; Stage #2: With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol at 30℃;
  • 72
  • [ 99-20-7 ]
  • [ 1486-48-2 ]
  • [ 1314875-96-1 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: TREHALOSE; 3,4,5-tribenzyloxybenzoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane Inert atmosphere; Reflux; Stage #2: With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol at 30℃;
80% Stage #1: TREHALOSE; 3,4,5-tribenzyloxybenzoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane Reflux; Inert atmosphere; Stage #2: With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol at 30℃;
  • 73
  • [ 99-20-7 ]
  • [ 760-93-0 ]
  • trehalose 6-O-methacrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE In dimethyl sulfoxide Inert atmosphere; Stage #2: methacryloyl anhydride With triethylamine In dimethyl sulfoxide at 21℃; for 17h; 11 Synthesis of Methacrylate Trehalose Monomer (TrMA) Trehalose was added to 10 mL of anhydrous dimethylsulfoxide (DMSO) under argon and stirred 10-15 minutes to dissolve. Triethylamine was added to the stirring solution before adding methacrylic anhydride dropwise. The solution was stirred for 17 h at 21 °C during which time it turned a faint clear yellow color. To purify, the reaction solution was added to ice cold 8:2 hexanes/DCM (200 mL) and stirred for 5-10 minutes. The organic layer was decanted, leaving a sticky solid on the bottom of the flask, which was re-dissolved in deionized water (20 mL). The remaining organic solvent was removed via rotary evaporator prior to HPLC purification (Cl 8 column, 20 ml/min flow, 10-60% MeOH, 20 min run). The product (C6 regioisomer), which had a retention time of 14 minutes, was collected and lyophilized to yield a white, fluffy solid. NMR (500 MHz, D20) d 6.06-6.01 (s, 1H, CHHCCH3), 5.65-5.61 (s, 1H, CHHCCH3), 5.08-5.02 (m, S8 2H, OCHO), 4.41-4.22 (m, 2H, COCH2CH), 3.99-3.36 (m, 10H, CH and CH20H), 1.84-1.80 (s, 3H, CH3) ppm; 13C NMR (500 MHz, DMSO-d6) d 166.9, 136.5, 126.3, 93.7, 93.6, 73.3, 73.1, 72.1, 72.0, 70.7, 70.5, 70.1, 64.3, 61.2, 18.4 ppm.
  • 74
  • [ 99-20-7 ]
  • [ 106-33-2 ]
  • trehalose monododecanoate [ No CAS ]
  • 6,6’-O-didodecanoyl-α,α’-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With novozyme 435 In water at 80℃; Green chemistry; Enzymatic reaction; Stage #2: ethyl laurate In diethyl ether Green chemistry; 2.2. General synthesis of sugar esters General procedure: Enzymatic synthesis of sugar esters under solvent-free conditionswas carried out using a modified method from Gelo-Pujic et al. [23].The sugar substrate (1 mmol) was dissolved in 2 mL of water in a 50 mLround bottle and then impregnated on Novozyme 435 (0.034, 0.17,0.34 and 0.68 g/mol of sugar substrate) by evaporating the aqueoussolution under a reduced pressure by heating in a water bath. Here, awater bath temperature of up to 80 °C was used.The lipid substrate (La or LaEt) (1, 2, 3 or 4 mmol) dissolved indiethyl ether (Et2O) was added to the dried mixture. Here, adding LaEtwithout Et2O was also tried for a comparative study. The Et2O in thereaction mixture was evaporated completely prior to starting the reaction.The content in the oil bath was heated at different temperatures(50, 60, 70, 80, 90, 100, 110, 120, 130 and 150 °C) and monitored forvarious reaction times (6, 12, 24, 48, 72 and 96 h). After the reactionmixtures were cooled down to ambient temperatures, they were extracted by N,N-dimethylformamide (DMF) at 60 °C under ultrasonicationtreatment. Some sugar esters such as trehalose monoester(TME), trehalose diester (TDE) and glucose monoester (GME) wereisolated via silica gel column chromatography using a mixed solventsystem [chloroform/methanol/acetone/water=9/4/4/1 (v/v/v/v)] asan eluent. The nuclear magnetic resonance (NMR) spectra of TME, TDEand GME were consistent with the reported data for 6-O-lauroyl trehalose,6,6′-O-dilauroyl trehalose and 6-O-lauroyl-α-D-glucopyranose[30-32] (Figure S1, Supplementary Material), and the obtained sampleswere of high purity.
  • 75
  • [ 99-20-7 ]
  • [ 98-88-4 ]
  • [ 142386-46-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With pyridine; trityl chloride at 40℃; for 16h; Stage #2: benzoyl chloride at 0 - 20℃; for 10h; Stage #3: With toluene-4-sulfonic acid In methanol; dichloromethane at 20℃; for 12h; 6 Example 6. Synthesis of amide linked aryl and alkyl trehalose compounds TrCl, Py, 40 °C, 16 hr; ii) PhCOCl, 0 °C to rt, 10 hr; Hi) TsOH-H20, CH2Cl2/MeOH (1 : 1), rt, 12 hr;
  • 76
  • [ 99-20-7 ]
  • [ 79-08-3 ]
  • C16H26O15 [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: TREHALOSE With sodium hydroxide In isopropyl alcohol at 40 - 60℃; for 1h; Stage #2: bromoacetic acid In isopropyl alcohol at 40℃; for 5h; 1.1 The first step, the preparation of trehalose dicarboxylic acid, the specific steps are as follows: at room temperature, trehalose (3g, 7.9mmol) is dissolved in 30ml of isopropanol, sodium hydroxide (2.4g, 60mmol) is added to the reaction solution, the temperature The control was stirred at 40-60 ° C for 1 h.Bromoacetic acid (2.75 g, 19.8 mmol) was added in small portions to the reaction mixture, and the mixture was heated at 40 ° C for 5 h.The room temperature was returned, the insoluble material was filtered and rinsed three times with a small amount of methanol.The white solid was transferred to 1M diluted hydrochloric acid and shaken for 10 min.The liquid was distilled off under reduced pressure and dried under vacuum for 12 h to give the product 3.07 g.
  • 77
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • [ 108-24-7 ]
  • 2,3,4,6,2',3'-hexa-O-acetyl-4',6'-O-benzylidene-α,α-D-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.6 g Stage #1: TREHALOSE; benzaldehyde dimethyl acetal With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40℃; for 12h; Stage #2: acetic anhydride With dmap; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; 2 2,3,2',3',4',6'-O-Acetyl-4,6-di-O-benzylidene-a-D-trehalose (7b). Benzaldehyde dimethyl acetal (1.62 mL, 10.8 mmol), trehalose (2054 mg, 6.0 mmol) and p- toluenesulfonic acid monohydrate (0.23 g, 1.2 mmol) were added to DMF (30 mL). The mixture was stirred for 12 hours at 40 °C. After cooling to 0 °C, triethylamine (23.60 g, 232.0 mol) and DMAP (122 mg, 1.00 mmol) were added followed by Ac2O (13.0 g, 116.0 mmol) dropwise. The reaction mixture was slowly warmed to RT and stirred overnight, after which it was poured into water, and extracted by ethyl acetate 3 times. The combined organic phase was washed by brine twice, and dried over Na2SO4. After removing the solvent, the residue was purified by column chromatography (ethyl acetate:hexanes = 1:1.5~1:1) twice to give the desired product as a white amorphous solid (1.60 g, 40%).1H NMR (500 MHz, CDCl3): d 7.48 - 7.38 (m, 2H, Ar-H), 7.38 - 7.30 (m, 3H, Ar-H), 5.61 (t, J = 9.8 Hz, 1H; H-3'), 5.55 - 5.44 (m, 2H; H-3, PhCH), 5.37 (d, J = 3.7 Hz, 1H; H-1'), 5.27 (d, J = 3.7 Hz, 1H; H-1), 5.09 - 5.02 (m, 2H; H-2' and H-4'), 5.00 (dd, J = 10.2, 4.0 Hz, 1H, H-2),4.25 (dd, J = 12.2, 5.6 Hz, 1H; H-6a'), 4.17 (dd, J = 10.5, 4.9 Hz, 1H; H-6a), 4.09 (ddd, J = 10.3, 5.7, 2.2 Hz, 1H; H-5'), 4.01 (dd, J = 12.2, 2.2, 1H; H-6b'), 3.97 (td, J = 9.9, 4.9 Hz, 1 H, H-5), 3.75 (t, J = 10.4 Hz; 1H, H-6b), 3.69 (t, J = 9.6 Hz, 1H; H-4), 2.22 - 1.96 (m, 18H; OAc).13C NMR (126 MHz, CDCl3) d 170.76, 170.22, 170.03, 169.97, 169.78, 169.78, 136.87, 129.32, 128.41, 126.34, 101.96, 93.49, 92.35, 79.16, 77.43, 70.78, 70.24, 70.16, 69.06, 68.70, 68.28, 63.34, 61.94, 21.01, 20.84, 20.79, 20.79.
  • 78
  • [ 99-20-7 ]
  • [ 112-61-8 ]
  • [ 64622-93-1 ]
YieldReaction ConditionsOperation in experiment
70% With potassium carbonate In 1,2-dimethoxyethane at 130℃; for 5h; Inert atmosphere; 1 16g methyl stearate and 150mL alcohol solvent ethylene glycol, build a vacuum distillation device, connect a vacuum water pump, add a magnet to start stirring, add dried 37g trehalose powder and 0.8g catalyst K2CO3 powder, vacuum distillation, The temperature was raised to 130°C, and the reaction was carried out for 5 hours under a vacuum of 0.09 Pa. During the reaction, the methanol produced by the reaction was distilled off. After cooling and filtering, 24 g of trehalose stearic acid monoester was obtained. The product yield of this example is 72%.
  • 79
  • [ 99-20-7 ]
  • [ 2186-92-7 ]
  • C28H34O13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; 1.1 1) Synthesis of compound 5 Dissolve trehalose (10.00g, 0.03mol) and p-toluenesulfonic acid monohydrate (1.10g, 5.84mol) in dimethylformamide,Add anisaldehyde dimethyl acetal (20mL, 0.117mol) dropwise under the protection of nitrogen, stir and react at room temperature. After 24 hours of reaction, Dilute with ethyl acetate, saturated sodium bicarbonate solution, let stand,A white solid precipitated, and it was filtered with suction to obtain compound 5 (11.90 g, 70%).
  • 80
  • [ 143-07-7 ]
  • [ 99-20-7 ]
  • trehalose monododecanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: TREHALOSE With chloro-trimethyl-silane; triethylamine In dichloromethane at 0 - 20℃; for 16h; Stage #2: With potassium carbonate In methanol; dichloromethane at 0 - 20℃; for 1.25h; Stage #3: lauric acid Further stages; 2.1 Synthesis of lactose monolaurate and trehalose monolaurate For the synthesis of C12-trehalose, triethylamine (130.9mmol) was added to a stirred suspension of trehalose (3.27mmol) in dichloromethane (DCM) (15mL). The reaction mixture was cooled to 0°C, and trimethylsilyl chloride (39.26mmol) was added. The solution was stirred at room temperature (RT) for 12h, and then an additional 13.08mol of trimethylsilyl chloride were added at 0°C. The reaction was left to stir for an additional 4h at RT and then the solvents were evaporated using a rotor to extract the crude product with petroleum ether. The organic layers were concentrated by vacuum to obtain a cream-yellow intermediate that was then solubilized in a cooled solution of methanol and DCM (19mL, 3:1) at 0°C. Potassium carbonate (0.40mmol) was added and the reaction was stirred for 15min at 0°C and then at RT for 1h. The reaction was quenched by the addition of acetic acid (0.7mL). The solvents were removed by vacuum and the product was purified by column chromatography before placement in a flame-dried Schlenk flask with 4-DMAP (1.30mmol) and lauric acid (1.30mmol) in 5mL of anhydrous DCM. A solution of 1,3-DCC (1.20mmol) in anhydrous DCM (3mL) was added dropwise. The mixture was left to react overnight at RT, under a nitrogen atmosphere. The resulting precipitate was removed by filtration under reduced pressure, washed with dichloromethane and purified by flash column chromatography. Finally, to obtain the ester, the intermediate was added to 0.5mL of a 3:1 DCM / methanol solution with 10% w/w of Dowex-H+. After 30min stirring at RT, the mixture was filtered and concentrated by vacuum, and the resulting residue was crystallized to obtain C12-trehalose. The purity of the synthesised C12-lactose and C12-trehalose was estimated from 1H NMR to be ≥95%, while Sigma’s data sheet specification for C12-sucrose states a value of ≥97%. The structures of the three esters are shown (Fig. 1 ).
  • 81
  • [ 75-77-4 ]
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • 2,3,2',3'-tetra-O-trimetylsilyl-4,6:4',6'-di-O-benzylidene-α,α'-trehalose [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: TREHALOSE With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 105℃; for 0.0833333h; Stage #2: benzaldehyde dimethyl acetal In N,N-dimethyl-formamide at 100℃; for 1.66667h; Stage #3: chloro-trimethyl-silane In N,N-dimethyl-formamide at 20℃; for 18h; 2,3,2',3'-Tetra-O-trimetylsilyl-4,6:4',6'-di-O-benzylidene-α,α'-trehalose 17 Trehalose dihydrate (1.43 g, 3.789 mmol, 1 eq) was dried under vacuum at 100°C overnight. Then, it was transferred in a two-neck round bottom flask and dissolved under argon atmosphere in dry DMF (9 mL). The mixture was heated at 105°C for 5 minutes, then solid p-toluenesulfonic acid monohydrate (36.1 mg, 0.190 mmol, 0.05 eq) was added and the solution was stirred for additional 5 minutes. Benzaldehyde dimethyl acetal (1.251 mL, 8.336 mmol, 2.2 eq) was added in three portions during 1 hour, while maintaining the reaction temperature at 100°C. Then, the solution was stirred for additional 40 minutes (TLC monitoring, eluant mixture: 95:5 DCM/MeOH). The brown solution was cooled at 0°C, and a solution of 1H-Imidazole (2.06 g, 30.312 mmol, 8 eq) in dry DMF (4 mL) was added dropwise. Then, trimethylsilyl chloride (2.9 mL, 22.716 mmol, 6 eq) was added dropwise, and the solution was stirred at RT for 18 hours (TLC monitoring, eluant mixture: 9:1 n-hexane/ EtOAc). The solvent was removed under high vacuum, and the crude solid was dissolved in EtOAc (70 mL). The organic layer was then sequentially washed with water (2 x 40 mL) and brine (30 mL). The organic layer was dried with Na2SO4 and concentrated under reduced pressure. The crude (3 g) was purified by flash chromatography (eluant mixture: from 95:5 to 85:15 n-hexane/ EtOAc) yielding 2.32 g of pure 17 as a white solid (2.879 mmol, 76% yield). Characterization:1H NMR (300 MHz, CDCl3): δ (ppm) 7.48 (m, 4H, Ph), 7.37 (m, 6H, Ph), 5.45 (s, 2H, H7), 4.92 (d, J=3.5 Hz, 2H, H1), 4.21-4.00 (m, 6H, H2, H3, H5), 3.70-3.52 (m, 4H, H4, H6), 3.41 (t, J=4.7 Hz, 2H, H6), 0.2 (s, 18H, TMS), 0.1 (s, 18H, TMS).
  • 82
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • [ 100-39-0 ]
  • [ 116594-37-7 ]
YieldReaction ConditionsOperation in experiment
33% Stage #1: TREHALOSE With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 105℃; for 0.0833333h; Inert atmosphere; Stage #2: benzaldehyde dimethyl acetal In N,N-dimethyl-formamide at 100℃; for 1.66667h; Stage #3: benzyl bromide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 24h; 2,3,2',3'-Tetra-O-acetyl-4,6:4',6'-di-O-benzylidene-α,α'-trehalose 39 Trehalose dihydrate 1 (1 g, 2.922 mmol, 1 eq) was dried under vacuum at 96°C overnight. Then it was transferred in a two-neck round bottom flask and dissolved under argon atmosphere in dry DMF (8 mL). The mixture was heated at 105°C for 5 minutes, then solid p-toluenesulfonic acid monohydrate (PTSA, 25.2 mg, 0.146 mmol, 0.05 eq) was added. The resulting solution was stirred for additional 5 minutes. Benzaldehyde dimethyl acetal (0.94 μL, 6.428 mmol, 2.2 eq) was then added in three equal portions in 1 hour, while maintaining the reaction temperature at 100°C. After the third addition the solution was stirred for additional 40 minutes, while monitoring by TLC (eluant mixture: DCM/MeOH 95:5). The solvent was removed at reduced pressure, the brown oily residue was dissolved in pyridine (10 mL) and cooled at 0°C under stirring. Then Ac2O (2.8 mL, 14.61 mmol, 10 eq) was slowly added and the solution was stirred at RT for 16 hrs (TLC monitoring, eluant mixture: n-hexane/EtOAc 6:4). After reaction completion, the solvent was removed at reduced pressure. The crude solid was dissolved in EtOAc (50 mL), and was sequentially washed with 5% aq. HCl (25 mL), sat. aq. NaHC03 (25 mL), and brine (15 mL). The organic layer was then dried with Na2SO4 and concentrated under reduced pressure. The crude (2.3 g) was purified by flash chromatography (eluant mixture: n-hexane/EtOAc from 7:3 to 1:1), yielding 1.65 g of pure 18 as a white solid (2.338 mmol, 80% yield). Characterization:1H NMR (300 MHz, CDCl3): δ (ppm) 7.50-7.31 (m, 10H, Ph), 5.62 (t, J=9.8 Hz, 2H, H3), 5.51 (s, 2H, H7), 5.32 (d, J=4.0 Hz, 2H, H1), 5.00 (dd, 2H, J=9.8 Hz, J=4.0 Hz, H2), 4.18 (m, 2H, H6), 4.00 (m, 2H, H5), 3.75 (m, 4H, H6, H4), 2.18 (s, 6H, Ac), 2.07 (s, 6H, Ac).
  • 83
  • [ 99-20-7 ]
  • [ 1125-88-8 ]
  • [ 108-24-7 ]
  • [ 161754-76-3 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: TREHALOSE With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 105℃; for 0.0833333h; Stage #2: benzaldehyde dimethyl acetal In N,N-dimethyl-formamide at 100℃; for 1.66667h; Stage #3: acetic anhydride In N,N-dimethyl-formamide at 20℃; for 16h; 2,3,2',3'-Tetra-O-acetyl-4,6:4',6'-di-O-benzylidene-α,α'-trehalose 39 Trehalose dihydrate 1 (1 g, 2.922 mmol, 1 eq) was dried under vacuum at 96°C overnight. Then it was transferred in a two-neck round bottom flask and dissolved under argon atmosphere in dry DMF (8 mL). The mixture was heated at 105°C for 5 minutes, then solid p-toluenesulfonic acid monohydrate (PTSA, 25.2 mg, 0.146 mmol, 0.05 eq) was added. The resulting solution was stirred for additional 5 minutes. Benzaldehyde dimethyl acetal (0.94 μL, 6.428 mmol, 2.2 eq) was then added in three equal portions in 1 hour, while maintaining the reaction temperature at 100°C. After the third addition the solution was stirred for additional 40 minutes, while monitoring by TLC (eluant mixture: DCM/MeOH 95:5). The solvent was removed at reduced pressure, the brown oily residue was dissolved in pyridine (10 mL) and cooled at 0°C under stirring. Then Ac2O (2.8 mL, 14.61 mmol, 10 eq) was slowly added and the solution was stirred at RT for 16 hrs (TLC monitoring, eluant mixture: n-hexane/EtOAc 6:4). After reaction completion, the solvent was removed at reduced pressure. The crude solid was dissolved in EtOAc (50 mL), and was sequentially washed with 5% aq. HCl (25 mL), sat. aq. NaHC03 (25 mL), and brine (15 mL). The organic layer was then dried with Na2SO4 and concentrated under reduced pressure. The crude (2.3 g) was purified by flash chromatography (eluant mixture: n-hexane/EtOAc from 7:3 to 1:1), yielding 1.65 g of pure 18 as a white solid (2.338 mmol, 80% yield). Characterization:1H NMR (300 MHz, CDCl3): δ (ppm) 7.50-7.31 (m, 10H, Ph), 5.62 (t, J=9.8 Hz, 2H, H3), 5.51 (s, 2H, H7), 5.32 (d, J=4.0 Hz, 2H, H1), 5.00 (dd, 2H, J=9.8 Hz, J=4.0 Hz, H2), 4.18 (m, 2H, H6), 4.00 (m, 2H, H5), 3.75 (m, 4H, H6, H4), 2.18 (s, 6H, Ac), 2.07 (s, 6H, Ac).
  • 84
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 76-83-5 ]
  • [ 75869-80-6 ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: TREHALOSE With pyridine at 50℃; for 0.5h; Inert atmosphere; Stage #2: trityl chloride at 90℃; for 24h; Stage #3: acetic anhydride at 20℃; for 16h; Inert atmosphere; 2,3,4,2',3',4'-Hexa-O-acetyl-6,6'-di-O-trityl-α,α-trehalose 40 Anhydrous trehalose 1 (501.2 mg, 1.46 mmol, 1eq) was stirred under nitrogen atmosphere in dry pyridine (5 mL) for 30 minutes at 50°C. Trityl chloride (TrCl, 1.426 g, 5.116 mmol, 3.5 eq) was then added, and the reaction mixture was stirred at 90°C (TLC monitoring, eluant mixture: EtOAc/MeOH 8:2). After 24 hrs the solution was cooled at RT, Ac2O (1.25 ml, 13.14 mmol, 9 eq) was slowly added, and the reaction mixture was stirred under nitrogen for 16 hrs (TLC monitoring, eluant mixture: EtOAc/n-hexane 3:7). Then the solvent was removed under reduced pressure. The crude solid was dissolved in EtOAc (30 mL), the organic layer was then sequentially washed with 5% aq. HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (10 mL). The organic layer was then dried with Na2SO4 and concentrated under reduced pressure. The crude was purified by flash chromatography (eluant mixture: EtOAc/n-hexane 3:7) yielding 1.13 g of pure 19 as a white solid (1.051 mmol, 72% yield).
  • 85
  • [ 99-20-7 ]
  • [ 108-24-7 ]
  • [ 42891-35-0 ]
  • [ 42891-34-9 ]
  • [ 25018-27-3 ]
YieldReaction ConditionsOperation in experiment
1: 25% 2: 20% 3: 50% Stage #1: TREHALOSE With triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: With N-Bromosuccinimide In N,N-dimethyl-formamide at 20 - 60℃; Inert atmosphere; Stage #3: acetic anhydride With pyridine at 0 - 20℃; 2,3,4,2',3',4',6'-Hepta-O-acetyl-6-bromo-6-deoxy-α,α-trehalose 13 and 2,3,4,2',3',4',-hexa-O-acetyl-6,6’-bromo-6,6’-deoxy-α,α-trehalose 14. Trehalose dihydrate (950 mg, 2.775 mmol, 1 eq) was dehydrated in vacuum at 100° overnight. Then it was dissolved under nitrogen atmosphere in dry DMF (9 mL), and solid Ph3P (1.456 g, 5.55 mmol, 2 eq) was added under stirring at RT. After 15 minutes, solid N-bromosuccinimide (NBS, 988 mg, 5.551 mmol, 2 eq) was added in small portions over 1 hour while stirring. The mixture was stirred at RT overnight, warmed to 60°C and stirred for additional 24 hours (TLC monitoring, eluant mixture: 60:35:5 CHCl3/MeOH/H2O). MeOH (10 mL) was then added to quench the reaction, and the solvents were removed under reduced pressure to give a yellow-brown solid (1.2 g). The residue was dissolved in water (50 mL), and the solution was washed with DCM (4x20 mL). The aqueous phase was then concentrated at reduced pressure. The resulting brown oil was dissolved in pyridine (9 mL), cooled at 0°C under stirring and acetic anhydride (3.7 mL, 38.85 mmol, 2 eq) was added dropwise. The reaction was stirred overnight at RT (TLC monitoring, eluant mixture: 8:2 DCM/EtOAc). After solvent removal at reduced pressure, the crude was dissolved in EtOAc (60 mL) and washed sequentially with 5% aq. HCl (30 mL), saturated aq. NaHCO3 (30 mL) and brine (30 mL). The organic phase was dried with Na2SO4. After solvent concentration at reduced pressure, column chromatography on silica gel (eluant mixture: from 9:1 to 8:2 DCM/EtOAc) led to pure 485.3 mg of 13 as a white solid (0.694 mmol, 25% yield) and 400 mg of pure 14 as a white solid (0.555 mmol, 20% yield).
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