* 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.
To a suspension of D-ribose (1; 20.0 g, 133.2 mmol) in acetone (100mL) and MeOH (100 mL) was carefully added conc. H2SO4 (10 mL) at r.t. The resulting solution was stirred for 48 h. After the completion of reaction by TLC monitoring, the solution was neutralized by the addition of solid NaHCO3. The solid was filtered, then the mixture was concentrated, and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, and the solvent was evaporated. The crude product was purified by silica gel flash column chromatography to give the product as a pale yellow oil; yield 24.4 g (90percent); Rf = 0.2 (hexane/EtOAc= 5:1, v/v); [α]D25 –80.00 (c 1.00, CHCl3) {Lit.26 [α]D20 –75.00 (c 1.00,CHCl3)}.1H NMR (CDCl3, 400 MHz): δ = 4.97 (s, 1 H), 4.83 (d, J = 5.7 Hz, 1 H),4.58 (d, J = 6.0 Hz, 1 H), 4.42 (t, J = 2.7 Hz, 1 H), 3.56–3.72 (m, 2 H),3.43 (s, 3 H), 3.32 (dd, J = 10.0, 3.0 Hz, 1 H), 1.49 (s, 3 H), 1.32 (s, 3 H).
46%
Stage #1: With hydrogenchloride In water for 1.5 h; Inert atmosphere; Reflux Stage #2: With pyridine In water at 20℃; Inert atmosphere
Compound5 was prepared from D-ribose according to literature procedures.1D-ribose (6.987 g, 46.07 mmol) was dissolved in a60 mL solution of 1:1 methanol/acetone. Approximately1 mL of concentrated HCl was added dropwise before reaction was heated toreflux for 90 min. The reaction was monitoredby TLC (2:1 EtOAc/hexanes) and allowed to cool to room temperature uponconsumption of starting material. Thereaction mixture was neutralized with pyridine and concentrated by rotaryevaporation. The crude material was partitionedbetween ethyl acetate (40 mL) and water (100 mL). The aqueous layer was extracted with threeportions of ethyl acetate (40 mL), and the organic layers were combined andwashed with saturated aqueous CuSO4 (75 mL), two portions of dH2O(75 mL), one portion of brine (75 mL), and dried over MgSO4. After filtration, the product was concentratedby rotary evaporation. Product wasisolated as a light yellow oil after short-path distillation (4.299 g, 21.05mmol, 46percent) but crude material (5.738 g, 28.1 mmol, 60percent) was typically used toprepare sulfonates 8d and 8e.
Reference:
[1] Synthesis (Germany), 2017, vol. 49, # 18, p. 4299 - 4302
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 7972 - 7990
[3] Journal of the American Chemical Society, 2015, vol. 137, # 10, p. 3558 - 3564
[4] Organic and Biomolecular Chemistry, 2009, vol. 7, # 4, p. 761 - 776
[5] Journal of Fluorine Chemistry, 1993, vol. 60, # 2.3, p. 239 - 250
[6] Journal of Organic Chemistry, 1996, vol. 61, # 18, p. 6175 - 6182
[7] Angewandte Chemie - International Edition, 2016, vol. 55, # 37, p. 11226 - 11230[8] Angew. Chem., 2016, vol. 128, # 37, p. 11392 - 11396,5
[9] Carbohydrate Research, 2014, vol. 394, p. 32 - 38
[10] Carbohydrate Research, 2010, vol. 345, # 1, p. 41 - 44
[11] Organic Letters, 2011, vol. 13, # 7, p. 1594 - 1597
[12] Organic and Biomolecular Chemistry, 2012, vol. 10, # 30, p. 6186 - 6200
[13] Synthesis (Germany), 2014, vol. 46, # 9, p. 1185 - 1190
[14] Patent: WO2018/167794, 2018, A1, . Location in patent: Page/Page column 62; 63
2
[ 532-20-7 ]
[ 67-64-1 ]
[ 4099-85-8 ]
Yield
Reaction Conditions
Operation in experiment
80%
With acetyl chloride In methanol for 12 h; Inert atmosphere; Reflux
AcCl(95 µL, 1.33 mmol) was addeddropwise to a solution of d-ribose(2.00 g, 13.33 mmol) in MeOH (8.0 mL) and Me2CO (8.0 mL). Thesolution was then heated at reflux for 12 h. The reaction was then quenchedwith sat. NaHCO3 (5mL) and the organic solvents evaporated under reduced pressure. The aqueoussolution was then extracted with EtOAc (2×20 mL), and the combined organicwashings dried over MgSO4, filtered and concentrated under reducedpressure to afford the desired compound as a colourless oil (2.18 g, 80percent), which was deemed sufficiently pure(according to 1H NMR spectroscopy) to be used in the nextreaction without further purification. Rf = 0.45 (2:1 hexanes/EtOAc). 1HNMR (300 MHz, CDCl3)d 4.97 (s, 1H), 4.84 (d, J = 5.9 Hz, 1H), 4.59 (d, J =5.9 Hz, 1H), 4.44 (t, J = 2.6 Hz,1H), 3.70 (dt, J = 12.6, 2.4 Hz, 1H),3.62 (ddd, J = 12.6, 10.7, 3.4 Hz,1H), 3.44 (s, 3H), 3.23 (dd, J =10.7, 2.6 Hz, 1H), 1.49 (s, 3H), 1.32 (s, 3H). The spectral data matched those reported previously.
Reference:
[1] European Journal of Organic Chemistry, 2001, # 16, p. 3089 - 3096
[2] Nucleosides, Nucleotides and Nucleic Acids, 2003, vol. 22, # 11, p. 2027 - 2038
[3] Patent: WO2005/20933, 2005, A2, . Location in patent: Page/Page column 52
[4] Croatica Chemica Acta, 2015, vol. 88, # 1, p. 43 - 52
4
[ 532-20-7 ]
[ 4099-85-8 ]
Reference:
[1] Organic Letters, 2004, vol. 6, # 20, p. 3461 - 3464
[2] Journal of Medicinal Chemistry, 2004, vol. 47, # 16, p. 4041 - 4053
[3] Carbohydrate Research, 1996, vol. 280, # 2, p. 209 - 221
[4] Chemistry--A European Journal, 2015, vol. 21, # 1, p. 126 - 135
5
[ 67-56-1 ]
[ 532-20-7 ]
[ 4099-85-8 ]
Reference:
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 24, p. 10079 - 10102
6
[ 2627-69-2 ]
[ 532-20-7 ]
[ 360-97-4 ]
Reference:
[1] Journal of Organic Chemistry, 1987, vol. 52, # 14, p. 3113 - 3119
7
[ 532-20-7 ]
[ 54622-95-6 ]
Reference:
[1] Journal of Medicinal Chemistry, 2004, vol. 47, # 16, p. 4041 - 4053
[2] Synthesis (Germany), 2017, vol. 49, # 18, p. 4299 - 4302
8
[ 532-20-7 ]
[ 15384-34-6 ]
Reference:
[1] Tetrahedron, 2008, vol. 64, # 42, p. 9989 - 9991
[2] Chemical Communications, 2017, vol. 53, # 75, p. 10362 - 10365
9
[ 93135-56-9 ]
[ 13754-19-3 ]
[ 532-20-7 ]
Reference:
[1] Journal of Organic Chemistry, 1984, vol. 49, # 25, p. 4964 - 4969
10
[ 550-33-4 ]
[ 13754-19-3 ]
[ 532-20-7 ]
[ 120-73-0 ]
Reference:
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1984, vol. 38, # 8, p. 673 - 678
11
[ 532-20-7 ]
[ 22423-26-3 ]
Reference:
[1] Journal of the Chemical Society, Chemical Communications, 1994, # 10, p. 1255 - 1256
[2] Journal of the Chemical Society, Chemical Communications, 1994, # 10, p. 1255 - 1256
12
[ 532-20-7 ]
[ 100-39-0 ]
[ 68-12-2 ]
[ 64363-77-5 ]
Yield
Reaction Conditions
Operation in experiment
90%
at 20℃; for 12 h; Cooling with ice
12 g (73.1mmol) of ribose was weighed and added to 250mL eggplant bottle, 160 mL of analytically pure DMF was added and 17g NaH was added in ice bath and 38 mL BnBr was dropped slowly. The temperature was slowly raised to room temperature, and reacted for 12 hours. After completion of the reaction by TLC, methanol was added slowly to extract the reaction and again extracted with EA, washed with water, and the crude product was chromatographed (PE: EA = 15: 1 → 9: 1) to give the compound (2R,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-5-methoxytetrahydrofuran (28.6 g, 65.8 mmol, 90percent). The compound 38a (3.5 g, 8.0 mmol) was weighed into a 100 mL eggplant flask, 28 mL of 1,4-dioxane was added to dissolve it, and 28 mL of 4N HCl was added. The temperature was refluxed for 3 hours. After completion of the reaction tracked by TLC, the reaction mixture was extracted with EA, washed with water, and then washed with saturated NaHCO3 solution and saturated NaCl solution. The crude product was chromatographed under reduced pressure (PE: EA = 5: 1 → 3.5: 1) to obtain (3S,5R)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol (2.9 g,6.9 mmol, 86percent).
Reference:
[1] Patent: CN106167475, 2016, A, . Location in patent: Paragraph 0018-0024
General procedure: Per-O-acetylation of natural carbohydrates catalyzed by pyridine followed literature procedure, with slight modifications.33 A mixture of the carbohydrate (1.0 mmol), Ac2O (1.9 mL; 20 mmol), and pyridine (3 mL) was stirred at 25 °C for 24 h. The reaction mixture was diluted with 5 mL of CH2Cl2 and the organic phase was washed with1 mol L-1 HCl (3 × 5 mL), saturated NaHCO3 (3 × 5 mL), and brine (5 mL). The solvent was dried with anhydrous Na2SO4 and evaporated to furnish the per-O-acetylated carbohydrate derivatives. Peracetylated carbohydrates where characterized as above and showed physical and spectral data in accordance with literature.37-41
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[1] Tetrahedron Letters, 2008, vol. 49, # 29-30, p. 4491 - 4493
[2] European Journal of Medicinal Chemistry, 2010, vol. 45, # 7, p. 2713 - 2718
[3] Asian Journal of Chemistry, 2014, vol. 26, # 14, p. 4367 - 4369
[4] Journal of the Brazilian Chemical Society, 2015, vol. 26, # 4, p. 755 - 764
[5] Organic and Biomolecular Chemistry, 2004, vol. 2, # 17, p. 2538 - 2546
[6] Organic Letters, 2010, vol. 12, # 20, p. 4624 - 4627
[7] Journal of the American Chemical Society, 2011, vol. 133, # 27, p. 10459 - 10472
15
[ 532-20-7 ]
[ 108-24-7 ]
[ 28708-32-9 ]
[ 4627-30-9 ]
Reference:
[1] Synthesis, 2009, # 11, p. 1834 - 1840
16
[ 532-20-7 ]
[ 3387-36-8 ]
Reference:
[1] Journal of the American Chemical Society, 1983, vol. 105, # 25, p. 7428 - 7435
17
[ 532-20-7 ]
[ 162204-20-8 ]
Reference:
[1] Patent: CN102212095, 2016, B,
18
[ 532-20-7 ]
[ 274693-53-7 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3598 - 3602
D-ribose (100 g, 666 mmol) and methanol (1000 mL) were introduced into a 2-L flask. Concentrated sulfuric acid (5.0 mL, 66.6 mmol) was slowly added dropwise thereto during ice cooling. The flask was heated to room temperature so as to cause a reaction at room temperature for 4 hours. Sodium acetate (16.4 g, 200 mmol) was added thereto for neutralization, followed by concentration under reduced pressure. Crude 1-O-methyl-D-ribofuranose (134 g; purity: 81%; yield: 100%) was obtained as a white turbid oily component. [NMR data] 1H-NMR(400MHz,D2O-d):delta(beta-anomer)3.38(s,3H),3.57-3.62(m,1H),3,76-3,80(m,1H),3.9 9-4.03(m, 2H),4.13-4.16(m,1H)4.89(d,J=1.0Hz,1H) (alpha-anomer)3.42(s,3H),3.63 -3.75(m,2H),3.98-4.1 (m,3H),4.98(d,J=4.5Hz;1H)
EXAMPLE 3.The synthesis of KTX 0312 by the esterification of arabinose with(RV-3-b.ydroxybutvric acid in the presence of CAL-B.; To a round-bottomed flask, lg arabinose and 5.5g 3-hydroxybutyric acid were added. The mixture was heated at 80C to obtain a homogenous solution. The temperature was lowered to 70C and 1.3g (20% w/v of the total mixture) CAl B was added. The mixture was stirred at 70C for 48 hrs to yield the arabinose 3-hydroxybutyrate di-and tri-esters as shown in Figure 3.The material was separated by column chromatography based on its polarity The column was packed in pure chloroform and the polarity was increased using memanol. The desired product was elutcd using ch.oroforro:methanol : water (9:2. 0.3).The product was a water-soluble syrup and was obtained at a yield of 0.2g (20%). A mixture of di- and tri-substituted products was formed (substitution factor 2 to 3 leaving 1 to 2 free hydroxyls per monosaccharide moiety. The structure of the compound was verified by LC/MS and by 'H NMR (300MHz, CDC13) and l3C NMR (75.5 MHz, CDCI3) spectroscopy
The chiral cyclopentenyl moiety 5 (below) was prepared from D-ribose in 8 steps following a previously reported synthetic method via a chiral induction, a regioselective protection of hydroxy group and ring-closing metathesis with 0.1 mole% of the 2nd generation Grubbs catalyst as key steps. 10; The other key intermediate 7 was synthesized according to the previously reported procedure11 from commercially available 4-amino-2-chloropyridine (6) in 4 steps (overall 54% yield) as shown in Scheme 1. Mitsunobu reaction of 7 with 5 provided a mixture of the N9- and N7-regioisomers (8:9 = 2:1) in 94% yield. The separation of the desired product (8) from the reaction mixture was difficult by silica gel column [isolated yields: 20% (8) and 20% (9), respectively]. The ratio of the two isomers was determined by 1H-NMR, and their configuration was identified by Nuclear Overhouser Effect (ID-NOE), which indicated the <n="38"/>interaction between the C1 '-H and the aromatic C3-H of compound 8, whereas the same effect was not present in compound 9.
With glycylglycine; phosphoenolpyruvic acid; potassium chloride; adenosine 5'-triphosphate disodium salt; magnesium chloride; diothiothreitol;adenylate kinase; pyruvate kinase; ribokinase; phospho-D-ribosyl-1-pyrophosphate synthase; PfOPRT; In water; at 37℃; for 20h;Enzymatic reaction;
Synthesis of Isotopically Labeled OMPs. [1'-3H]OMP, [1'-14C]OMP and [2'-3H]OMP were prepared enzymatically from [1-3H]ribose, [1-14C]ribose and [2-3H]ribose, respectively. [4'-3H]OMP, [5'-3H2]OMP and [5'-14C]OMP were synthesized from [5-3H]glucose, [6-3H2]glucose-6-phosphate and [6-14C]glucose, respectively. [3-15N]OMP and [1, 3-15N2]OMP were synthesized with [3-15N]- and [1, 3-15N2]<strong>[65-86-1]orotic acid</strong> as precursors, respectively (e.g. FIG. 3).Synthesis of OMP from ribose and orotate used a reaction mixture with 2.5 mM orotate, 1 mM ribose, 100 mM phosphate (pH=7.4), 50 mM glycylglycine, 50 mM KCl, 20 mM MgCl2, 20 mM phosphoenolpyruvate, 1 mM ATP and 2 mM DTT. The reactions were initialized by adding an enzyme mixture containing 1 unit AK, 1 unit PK, 0.01 unit RK, 0.008 unit PRPPase and 0.033 unit PfOPRT. This reaction mixture was incubated at 37 C. for 20 hr to reach completion. OMP products were then purified twice by reverse phase HPLC (C-18 Deltapak column, 20 mM KH2PO4, 8 mM tetrabutylammonium, pH=6.0 as eluting buffer). The OMPs were concentrated and repurified by HPLC, eluted with 2% (v/v) MeOH/H2O. The overall yields of OMP varied from 40% and 90% with reference to ribose.For OMP synthesis from glucose, the reactions contained 2.5 mM orotate, 1 mM glucose, 100 mM phosphate, 50 mM glycylglycine, 50 mM KCl, 20 mM MgCl2, 5 mM NH4C1, 20 mM phosphoenolpyruvate, 1 mM ATP, 0.1 mM NADP+, 20 mM alpha-keto glutarate and 2 mM DTT (pH=7.4). The reaction was initialized by adding 1 unit HK, 1 unit G6PDH, 0.075 unit PGDH, 0.02 unit PRI, 1 unit GDH, 0.016 unit PRPPase, 0.033 unit PfOPRT, 1 unit AK and 1 unit PK (pre-mixed enzyme solution). The reaction mixture was then incubated at 37 C. for 20 hr to generate OMP. The OMP products were purified as described above. The overall yields of OMP were 30% to 70% from starting glucose. After the last step of HPLC purification (described above), isotopically labeled OMPs were lyophilized, dissolved in H2O and stored at -80 C. for further use.
With hydrogen; at 184.84℃; under 20 Torr; for 24h;Autoclave;
The hydrolytic hydrogenation experiments were performed in a 300 ml Parr autoclave connected to a pre-reactor with a 200 ml volume. The autoclave was provided with a 1 mum filtered sampling outlet, which prevented the small catalyst particles from passing through it. The temperature was measured with a thermocouple and controlled automatically (Brooks Instrument). 600 mg of arabinogalactan was dissolved in 150 ml of deionized water and loaded to the pre-reactor. 300 mg of the catalyst with a particle size below 63 mum was loaded into the reactor. The amount of the catalyst loading was chosen on the basis of the quantity used in the previous study on the hydrolytic hydrogenation of cellulose [12], in order to facilitate a direct comparison between the hydrolytic hydrogenation of cellulose and hemicelluloses under similar reaction conditions. 20 bar of hydrogen pressure was applied and the solution was heated to 458 K. The stirring rate was 1145 rpm to minimize external diffusion affecting activity measurements. When the reactor had reached the desired temperature, stirring was applied and the arabinogalactan solution from the pre-reactor was fed into the reactor. This was considered as the initial reaction time. Liquid samples were periodically withdrawn at different times for analysis.
With hydrogen; at 184.84℃; under 20 Torr; for 24h;Autoclave;
The hydrolytic hydrogenation experiments were performed in a 300 ml Parr autoclave connected to a pre-reactor with a 200 ml volume. The autoclave was provided with a 1 mum filtered sampling outlet, which prevented the small catalyst particles from passing through it. The temperature was measured with a thermocouple and controlled automatically (Brooks Instrument). 600 mg of arabinogalactan was dissolved in 150 ml of deionized water and loaded to the pre-reactor. 300 mg of the catalyst with a particle size below 63 mum was loaded into the reactor. The amount of the catalyst loading was chosen on the basis of the quantity used in the previous study on the hydrolytic hydrogenation of cellulose [12], in order to facilitate a direct comparison between the hydrolytic hydrogenation of cellulose and hemicelluloses under similar reaction conditions. 20 bar of hydrogen pressure was applied and the solution was heated to 458 K. The stirring rate was 1145 rpm to minimize external diffusion affecting activity measurements. When the reactor had reached the desired temperature, stirring was applied and the arabinogalactan solution from the pre-reactor was fed into the reactor. This was considered as the initial reaction time. Liquid samples were periodically withdrawn at different times for analysis.
methyl (2-((3S,5S,6S,7S)-7-((R)-1,2-dihydroxyethyl)-5-((2-ethoxy-2-oxoethyl)carbamoyl)-6-hydroxy-2-oxo-1,4-oxazepan-3-yl)acetyl)-L-phenylalaninate[ No CAS ]
General procedure: The intermediate 3a-d (1.0 mmol) was dissolved in dichloromethane (10.0 mL), which has been dried through refluxing, under nitrogen atmosphere. Then, DMAP (1.5 mmol), EDCI (1.25mmol) were added to it in order. Then, ethylene glycol (0.5 mmol), glycerin (0.3 mmol), ribose (0.25 mmol) or xylose (0.25 mmol) was added. After stirring for 24 h at room temperature, the mixture was poured into water and washed with 1 mol/L HCl. The CH2Cl2 layer was concentrated, and the residue was purified using flash chromatography (ethyl acetate: Petroleum ether, 1:100-1:20) to obtain 4-6a, 4-7c or 4-7d. Compound 6-7a, 4-7b, 6d were used directly in the next step without purification and structural characterization.