[ CAS No. 3705-42-8 ] {[proInfo.proName]}

Name: 3705-42-8|Z-Glu-OBzl|97%
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2D 3D

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Quality Control of [ 3705-42-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 3705-42-8 ]

SDS Specification

Alternatived Products of [ 3705-42-8 ]

Product Details of [ 3705-42-8 ]

CAS No. :	3705-42-8	MDL No. :	MFCD00077013
Formula :	C₂₀H₂₁NO₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	371.38	Pubchem ID :	-
Synonyms :	Z-Glu-OBzl

Calculated chemistry of [ 3705-42-8 ]

Physicochemical Properties

Num. heavy atoms :	27
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.25
Num. rotatable bonds :	12
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	97.08
TPSA :	101.93 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.62 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.79
Log Po/w (XLOGP3) :	2.74
Log Po/w (WLOGP) :	2.59
Log Po/w (MLOGP) :	2.3
Log Po/w (SILICOS-IT) :	2.68
Consensus Log Po/w :	2.62

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.41
Solubility :	0.146 mg/ml ; 0.000393 mol/l
Class :	Soluble
Log S (Ali) :	-4.54
Solubility :	0.0108 mg/ml ; 0.0000292 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.33
Solubility :	0.00173 mg/ml ; 0.00000467 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.53

Safety of [ 3705-42-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 3705-42-8 ]

* 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.

Upstream synthesis route of [ 3705-42-8 ]
Downstream synthetic route of [ 3705-42-8 ]

[ 3705-42-8 ] Synthesis Path-Upstream 1~15

1
[ 4124-76-9 ]
[ 5680-86-4 ]
[ 3705-42-8 ]

Reference： [1] Chemische Berichte, 1933, vol. 66, p. 1288,1290

2
[ 3705-42-8 ]
[ 2419-56-9 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1964, vol. 673, p. 196 - 207

3
[ 3705-42-8 ]
[ 13030-09-6 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1962, vol. 655, p. 195 - 210

4
[ 100-51-6 ]
[ 4124-76-9 ]
[ 3705-42-8 ]

Reference： [1] J. Gen. Chem. USSR (Engl. Transl.), 1962, vol. 32, p. 2076 - 2080[2] Zhurnal Obshchei Khimii, 1962, vol. 32, # 7, p. 2102 - 2107
[3] Chemische Berichte, 1962, vol. 95, p. 7 - 16
[4] Chemische Berichte, 1963, vol. 96, p. 204 - 212
[5] Journal of the American Chemical Society, 1969, vol. 91, p. 2758 - 2765
[6] Chemische Berichte, 1964, vol. 97, p. 2434 - 2438
[7] Tetrahedron Letters, 2017, vol. 58, # 16, p. 1604 - 1606

5
[ 1155-62-0 ]
[ 100-51-6 ]
[ 3705-42-8 ]

Reference： [1] ChemBioChem, 2012, vol. 13, # 9, p. 1319 - 1326

6
[ 13030-09-6 ]
[ 501-53-1 ]
[ 3705-42-8 ]

Reference： [1] Journal of the American Chemical Society, 1953, vol. 75, p. 4608

7
[ 56-86-0 ]
[ 3705-42-8 ]

Reference： [1] Journal of the American Chemical Society, 1953, vol. 75, p. 4608
[2] Tetrahedron Letters, 2017, vol. 58, # 16, p. 1604 - 1606

8
[ 2768-50-5 ]
[ 3705-42-8 ]

Reference： [1] Journal of the American Chemical Society, 1953, vol. 75, p. 4608

9
[ 3967-18-8 ]
[ 3705-42-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 8, p. 2651 - 2655

10
[ 3886-08-6 ]
[ 3705-42-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 8, p. 2651 - 2655

11
[ 1155-62-0 ]
[ 3705-42-8 ]

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 16, p. 1604 - 1606

12
[ 501-53-1 ]
[ 3705-42-8 ]

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 16, p. 1604 - 1606

13
[ 4124-76-9 ]
[ 5680-86-4 ]
[ 3705-42-8 ]

Reference： [1] Chemische Berichte, 1933, vol. 66, p. 1288,1290

14
[ 53363-74-9 ]
[ 3705-42-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1962, vol. 655, p. 195 - 210

15
[ 1155-62-0 ]
[ 100-39-0 ]
[ 3705-42-8 ]

Reference： [1] Journal of the Chemical Society [Section] C: Organic, 1967, p. 2410 - 2421
[2] Recueil des Travaux Chimiques des Pays-Bas, 1964, vol. 83, p. 199 - 207

[ 3705-42-8 ] Synthesis Path-Downstream 1~86

1
[ 13030-09-6 ]
[ 501-53-1 ]
[ 3705-42-8 ]

Reference： [1]Journal of the American Chemical Society,1953,vol. 75,p. 4608

2
[ 4124-76-9 ]
[ 5680-86-4 ]
[ 3705-42-8 ]

Reference： [1]Chemische Berichte,1933,vol. 66,p. 1288,1290

3
[ 16305-80-9 ]
[ 3705-42-8 ]
α-Benzyl-N-benzyloxycarbonyl-L-glutamyl-L-α-amino-butyryl-glycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	(i) ClCO₂Et, Et₃N, THF, (ii) /BRN= 1724068/, Et₃N, H₂O; Multistep reaction;

Reference： [1]Ogata; Ishii [Chemical and pharmaceutical bulletin, 1967, vol. 15, # 5, p. 707 - 710]

4
[ 3705-42-8 ]
[ 42854-62-6 ]
[ 97154-87-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1962,vol. 655,p. 195 - 210

5
[ 3705-42-8 ]
[ 1738-76-7 ]
[ 98271-07-9 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1962,vol. 655,p. 195 - 210

6
[ 3705-42-8 ]
[ 13030-09-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1962,vol. 655,p. 195 - 210

7
[ 100-51-6 ]
[ 4124-76-9 ]
[ 3705-42-8 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 20℃; for 8h;Reflux;	To a solution of L-glutamic acid (5.0 g, 34.0 mmol) in saturated NaHCO3 aq. (113 mL)was added CbzCl (7.3 mL, 51.0 mmol) at 0oC and then the mixture was stirred for 2 h at room temperature. The reaction mixture was added to Et2O and 1M HCl and extracted with AcOEt. The organic layer was washed with H2O and brine, dried over MgSO4, and evaporated under reduced pressure to give crude Cbz-Glu-OH as a white solid. To the residue was added Ac2O (30 mL) at 0oC and then the mixture was stirred for over night at room temperature. The reaction mixture was evaporated under reduced pressure to give crude N-benzyloxycarbonyl glutamic anhydride as an oil. To the residue in toluene(153 mL) was added BnOH (4.8 mL, 46.2 mmol) at room temperature and then the mixture was heated to reflux. After the stirring for 8 h, saturated NaHCO3 aq. was added to the reaction mixture and the resulting solution was washed with Et2O. The aqueous phase is acidified to pH 1 with 1M HCl and extracted with AcOEt. The organic phase was washed with H2O, brine, dried over MgSO4 and evaporated under reduced pressure to give crude product (8.91 g) as red oil. To the crude product (2.40 g, 6.5 mmol)in THF (65 mL) were added EtOCOCl (1.9 mL, 19.5 mmol) and Et3N (2.7 mL, 19.5mmol) at -15oC. After the stirring for 2 h, NaBH4 (733 mg, 19.5 mmol) and H2O (223mL) were added to the solution at same temperature. The reaction mixture was stirred for 2 h and then neutralized with 1M KHSO4. The organic solvents were evaporated and the product was extracted with AcOEt. The organic phase was washed with H2O and brine, dried over MgSO4, and the solvent was evaporated. The residue was purified by column chromatography (Hexane:AcOEt = 2:1~1:1) to afford 7 (rotamer ratio = 3:1)(1.76 g, 4.9 mmol, 53%, 4 steps) as a white solid.

Reference： [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 2076 - 2080
Zhurnal Obshchei Khimii,1962,vol. 32,p. 2102 - 2107
[2]Chemische Berichte,1962,vol. 95,p. 7 - 16
[3]Chemische Berichte,1964,vol. 97,p. 2434 - 2438
[4]Tetrahedron Letters,2017,vol. 58,p. 1604 - 1606

8
[ 3705-42-8 ]
[ 760-84-9 ]
[ 94119-89-8 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 3421 - 3424

9
[ 3705-42-8 ]
[ 130096-70-7 ]

Yield	Reaction Conditions	Operation in experiment
40%		Cupric acetate monohydrate (2.26 g, 11.3 mmol) was added to a suspension of (S)-5-benzyloxy-4-(benzyloxycarbonylamino)-5-oxopentanoic acid (17) (21.0 g, 56.6 mmol) in dry benzene (500 mL). The mixture was stirred at room temperature for 1 h under argon. Freshly purified lead tetraacetate (50.1 g, 113 mmol) was added, and the mixture was stirred for another 1 h at room temperature. The mixture was heated under reflux for 12 h. After filtering the reaction mixture through Celite, the filtrate was diluted with ethyl acetate (1000 mL) and was washed three times with H2O and once with sat. NaCl. The organic layer was dried over anhydrous Na2SO4. After removal of solvent in vacuo, the residue was purified by flash column chromatography (10% ethyl acetate in hexane) to afford the (S)-vinylglycine derivative 18 (7.41 g, 40%) as a colorless solid. 1H-NMR (300 MHz, CDCl3): deltaH 7.41-7.27 (m, 10H, 2 Ph), 5.92 [ddd, J = 16.8, 10.2 and 5.4 Hz, 1H, CHCH=CH2] 5.47 (br d, J = 7.5, 1H, NH), 5.36 (dd, J =16.8 and 1.5 Hz) and 5.27 (dd, J =10.2 and 1.5 Hz) (2H, CH=CH2), 5.19 and 5.12 (2 s, 4H, 2 PhCH2O), 4.99 [dd, J = 7.5 and 5.4 Hz, 1H, NH(CO)CHCH=CH2]. IR (NaCl) 3313 (br), 3033, 1743, 1508, 1456, 1338, 1267, 1213, 1176, 1076, 1051, 989, 924, 737, 696 cm-1. Anal. calcd for C19H19NO4: C, 70.14; H, 5.89; N, 4.31. Found: C, 70.27; H, 5.98; N. 4.29.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1176 - 1194
[2]Organic Letters,2005,vol. 7,p. 2385 - 2388
[3]Journal of Organic Chemistry,1991,vol. 56,p. 728 - 731

10
[ 3705-42-8 ]
[ 71389-33-8 ]

Reference： [1]Journal of Organic Chemistry,1983,vol. 48,p. 741 - 744

11
[ 3705-42-8 ]
Z-Glu(F)-OBn [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 6371 - 6373

12
[ 3705-42-8 ]
[ 51145-58-5 ]
N-(benzyloxycarbonyl)-L-glutamic acid 1-(benzyl ester) 5-[(4-benzyloxy-phenyl)-hydrazide] [ No CAS ]

Reference： [1]Angewandte Chemie,1985,vol. 97,p. 1063 - 1064

13
[ 6066-82-6 ]
[ 3705-42-8 ]
[ 34897-67-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide; In 1,4-dioxane;	O-a-benzyl-N-a-(benzyloxycarbonyl)-L-?-glutamyl-S-triphenylmethyl-L-cysteinyl-2-phenyl-(2R)-glycine may be prepared by standard methods of peptide synthesis. A convenient synthesis, using the readily available starting materials N-a-(benzyloxycarbonyl)-L-?-glutamic acid a-benzyl ester, S-triphenylmethyl-L-cysteine, and D-phenylglycine, is as follows. N-a-(benzyloxycarbonyl)-L-?-glutamic acid a-benzyl ester is activated as the N-hydroxysuccinimide ester by reaction with N-hydroxysuccinimide and dicyclohexylcarbodiimide in anhydrous 1,4-dioxane. The N-a-(benzyloxycarbonyl)-L-?-glutamic acid a-benzyl ester ?-N-hydroxysuccinimide ester is dissolved in anhydrous tetrahydrofuran, and added to a solution of S-triphenylmethyl-L-cysteine and triethylamine in water to give O-a-benzyl-N-a-(benzyloxycarbonyl)-L-?-glutamyl-S-triphenylmethyl-L-cysteine. This is activated as the N-hydroxysuccinimide ester and coupled with D-phenylglycine in the same way as for the ?-glutamine-cysteine coupling to give the desired O-a-benzyl-N-a-(benzyloxycarbonyl)-L-?-glutamyl-S-triphenylmethyl-L-cysteinyl-2-phenyl (2R)-glycine.
	With dicyclohexyl-carbodiimide; In 1,2-dimethoxyethane; at 0 - 20℃; for 4h;	A stirred solution of N-Cbz Benzyl amino acid (N-Cbz Glutamine, 1.0 equiv) and N-hydroxysuccinimide (HOSu, 1.0 equiv) in DME (15 mL) was cooled to 0 C. Dicyclohexylcarbodiimide (DIC, 1.0 equiv) was added and stirred at this temperature for 4 hr. The reaction mixture was allowed to stand for 2 hr in a refrigerator and then filtered. As expected, the pure compound was obtained in excellent yield (98%) after filtration of the dicyclohexylurea (DCU) formed and evaporation of the solvent. The residue was triturated in Et2O/hexanes, filtered out, and then dried in vacuo to afford a white solid. The (+)-S-tritylcysteine lithium salt (H-Cys(STrt)-OLi, 1.0 equiv) and sodium carbonate (Na2CO3, 5.0 equiv) were dissolved in water (15 mL), and then acetonitrile (CH3CN) was added followed by the intermediated product obtained in Step-2. The mixture was vigorously stirred at room temperature for 3-6 hr until the TLC analysis indicated the absence of intermediated product in Step-2. The solution was washed with water (2100 mL) and the organic phase was dried with Na2SO4, filtered, and concentrated in vacuo to afford the compound 2. A stirred solution of compound 2 and N-hydroxysuccinimide (HOSu, 1.0 equiv) in DME (15 mL) was cooled to 0 C. Dicyclohexylcarbodiimide (DIC, 1.0 equiv) was added and stirred at this temperature for 4 hr. The reaction mixture was allowed to stand for 2 hr in a refrigerator and then filtered. After the DCU and solvent was removed, the glycine lithium salt (H-Gly-OLi, 1.0 equiv) and sodium carbonate (Na2CO3, 5.0 equiv) were dissolved in water (15 mL), and then acetonitrile (CH3CN) was added followed by the intermediated product obtained in Step-4. The mixture was vigorously stirred at room temperature for 3-6 hr until the TLC analysis indicated the absence of intermediated product in Step-4. The solution was washed with water (2100 mL) and the organic phase was dried with Na2SO4, filtered, and concentrated in vacuo to afford the compound 3. The d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS-OH) was coupling with compound 3 via esterification to afford the compound 4. The compound 4 in methanol (100 mL) was added 10% Pd-C (0.2 times the weight of protected tripeptide-TPGS) . The suspension was stirred at room temperature for 16 hr under a balloon filled with hydrogen. The suspension was filtered through Celite and evaporated, and the residue was crystallized from ethanol. Then, the compound 5 was obtained. Triethylsilane (Et3SiH) and TFA-mediated deprotection of compound 5 in the presence of CH2Cl2 provided the compound 6 (that is GSH-TPGS).
	With dicyclohexyl-carbodiimide; In 1,2-dimethoxyethane; at 0℃; for 4h;	A stirred solution of N-Cbz Benzyl amino acid (N-Cbz Glutamine, 1.0 equiv) and N-hydroxysuccinimide (HOSu, 1.0 equiv) in DME (15mL) was cooled to 0C. Dicyclohexylcarbodiimide (DIC, 1.0 equiv) was added and stirred at this temperature for 4hr. The reaction mixture was allowed to stand for 2hr in a refrigerator and then filtered. As expected, the pure compound was obtained in excellent yield (98%) after filtration of the dicyclohexylurea (DCU) formed and evaporation of the solvent. The residue was triturated in Et2O/hexanes, filtered out, and then dried in vacuo to afford a white solid. The (+)-S-tritylcysteine lithium salt (H-Cys(STrt)-OLi, 1.0 equiv) and sodium carbonate (Na2CO3, 5.0 equiv) were dissolved in water (15mL), and then acetonitrile (CH3CN) was added followed by the intermediated product obtained in Step-2. The mixture was vigorously stirred at room temperature for 3-6hr until the TLC analysis indicated the absence of intermediated product in Step-2. The solution was washed with water (2100mL) and the organic phase was dried with Na2SO4, filtered, and concentrated in vacuo to afford the compound 2. A stirred solution of compound 2 and N-hydroxysuccinimide (HOSu, 1.0 equiv) in DME (15mL) was cooled to 0C. Dicyclohexylcarbodiimide (DIC, 1.0 equiv) was added and stirred at this temperature for 4hr. The reaction mixture was allowed to stand for 2hr in a refrigerator and then filtered. After the DCU and solvent was removed, the glycine lithium salt (H-Gly-OLi, 1.0 equiv) and sodium carbonate (Na2CO3, 5.0 equiv) were dissolved in water (15mL), and then acetonitrile (CH3CN) was added followed by the intermediated product obtained in Step-4. The mixture was vigorously stirred at room temperature for 3-6hr until the TLC analysis indicated the absence of intermediated product in Step-4. The solution was washed with water (2100mL) and the organic phase was dried with Na2SO4, filtered, and concentrated in vacuo to afford the compound 3. The d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS-OH) was coupling with compound 3 via esterification to afford the compound 4. The compound 4 in methanol (100mL) was added 10% Pd-C (0.2 times the weight of protected tripeptide-TPGS). The suspension was stirred at room temperature for 16hr under a balloon filled with hydrogen. The suspension was filtered through Celite and evaporated, and the residue was crystallized from ethanol. Then, the compound 5 was obtained. Triethylsilane (Et3SiH) and TFA-mediated deprotection of compound 5 in the presence of CH2Cl2 provided the compound 6 (that is GSH-TPGS).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 253 - 258
[2]Agricultural and Biological Chemistry,1980,vol. 44,p. 2419 - 2424
[3]Patent: US2006/135409,2006,A1 .Location in patent: Page/Page column 9
[4]Patent: US2007/141133,2007,A1 .Location in patent: Page/Page column 2-3
[5]Patent: EP1891962,2008,A1 .Location in patent: Page/Page column 4-5

14
[ 3705-42-8 ]
[ 2791-84-6 ]
[ 7365-90-4 ]

Reference： [1]Agricultural and Biological Chemistry,1980,vol. 44,p. 2419 - 2424

15
[ 13030-09-6 ]
[ 3705-42-8 ]
[ 34897-64-8 ]

Reference： [1]Chemische Berichte,1962,vol. 95,p. 7 - 16

16
[ 3705-42-8 ]
[ 881883-91-6 ]

Reference： [1]Chemische Berichte,1964,vol. 97,p. 2434 - 2438
[2]Journal of Organic Chemistry,1999,vol. 64,p. 7467 - 7473

17
[ 3705-42-8 ]
[ 29390-67-8 ]
6¹-(N⁵-L-O¹-benzyl-N²-benzyloxycarbonyl-glutamino)-6¹-deoxycyclomaltoheptaose [ No CAS ]

Reference： [1]Carbohydrate Research,1997,vol. 303,p. 229 - 232

18
[ 3144-09-0 ]
[ 3705-42-8 ]
[ 247904-30-9 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

19
[ 3705-42-8 ]
[ 295788-09-9 ]
[ 295788-11-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1585 - 1588

20
[ 110-85-0 ]
[ 3705-42-8 ]
[ 485756-16-9 ]

Reference： [1]Synthesis,2002,p. 1398 - 1406

21
[ 296-35-5 ]
[ 3705-42-8 ]
1,4,7,10,13,16-hexakis[4'-(N-benzyloxycarbonyl)amino-4'-benzyloxycarbonylbutanoyl]hexaazacyclooctadecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃; for 24h;

Reference： [1]Liu, Cuihua; Hudson, Robert H. E.; Petersen, Nils O. [Synthesis, 2002, # 10, p. 1398 - 1406]

22
[ 295-64-7 ]
[ 3705-42-8 ]
1,4,7,10,13-pentakis[4'-(N-benzyloxycarbonyl)amino-4'-benzyloxycarbonylbutanoyl]pentaazacyclopentadecane [ No CAS ]

Reference： [1]Synthesis,2002,p. 1398 - 1406

23
[ 3705-42-8 ]
[ 294-90-6 ]
1,4,7,10-tetrakis[4'-(N-benzyloxycarbonyl)amino-4'-benzyloxycarbonylbutanoyl]tetraazacyclododecane [ No CAS ]

Reference： [1]Synthesis,2002,p. 1398 - 1406

24
[ 3705-42-8 ]
[ 4730-54-5 ]
1,4,7-tris[4'-(N-benzyloxycarbonyl)amino-4'-benzyloxycarbonylbutanoyl]triazacyclononane [ No CAS ]

Reference： [1]Synthesis,2002,p. 1398 - 1406

25
[ 3705-42-8 ]
[ 159339-55-6 ]
[ 511545-41-8 ]

Reference： [1]Australian Journal of Chemistry,2002,vol. 55,p. 635 - 645

26
[ 3705-42-8 ]
[ 167986-15-4 ]
[ 511545-43-0 ]

Reference： [1]Australian Journal of Chemistry,2002,vol. 55,p. 635 - 645

27
[ 3705-42-8 ]
[ 167986-16-5 ]
N^α-[N-(benzyloxycarbonyl)-L-(α-benzyloxy)glutamoyl]-N-[1-hydroxymethyl-2-[(1-oxohexadecyl)oxy]-1-[(1-oxohexadecyl)oxymethyl]ethyl]glycinamide [ No CAS ]

Reference： [1]Australian Journal of Chemistry,2002,vol. 55,p. 635 - 645

28
[ 3705-42-8 ]
[ 167986-17-6 ]
[ 511545-47-4 ]

Reference： [1]Australian Journal of Chemistry,2002,vol. 55,p. 635 - 645

29
[ 3705-42-8 ]
(E)-(S)-2-Amino-6-oxo-dec-4-enoic acid benzyl ester [ No CAS ]
(E)-(S)-2-((S)-4-Benzyloxycarbonyl-4-benzyloxycarbonylamino-butyrylamino)-6-oxo-dec-4-enoic acid benzyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 6501 - 6504

30
[ 75-91-2 ]
[ 3705-42-8 ]
2-benzyloxycarbonylamino-4-tert-butylperoxycarbonyl-butyric acid benzyl ester [ No CAS ]

Reference： [1]Organic Letters,2003,vol. 5,p. 2963 - 2965

31
[ 10027-74-4 ]
[ 3705-42-8 ]
[ 592532-02-0 ]

Reference： [1]Organic Letters,2003,vol. 5,p. 2963 - 2965

32
[ 3705-42-8 ]
[ 37517-78-5 ]
[ 608535-19-9 ]

Yield	Reaction Conditions	Operation in experiment
90%		N-Cbz-l-Glu-O-Bn (10.0 g, 27 mmol, 1.0 equiv) was dissolved in dry THF (100 mL) and treated with 1,1?-carbonyldiimidazole (5.69 g, 35 mmol, 1.3 equiv) and the mixture was stirred at room temperature for 2 h. Separately, potassium monoethylmalonate (6.8 g, 40 mmol) was dissolved in water (25 mL) and treated with concentrated hydrochloric acid (6 mL) and NaCl (11 g). The mixture was extracted with EtOAc (5 × 25 mL) and the combined EtOAc layers dried over Na2SO4, filtered and evaporated. The free acid of monoethylmalonate thus obtained was then directly dissolved in dry THF (80 mL), treated with magnesium ethoxide (2.9 g, 25 mmol), and stirred at room temperature for 1 h to generate magnesium monoethylmalonate. The fresh solution of magnesium monoethylmalonate in THF was then directly added to CDI-activated glutamatic acid species and the mixture stirred at room temperature for 16 h. The volume of the reaction mixture was next reduced to ca. 50 mL after which Et2O (300 mL) and 1 M HCl (100 mL) were slowly added. The layers were separated and the Et2O layer washed with 1 M HCl (1 × 100 mL), 5% NaHCO3 (3 × 100 mL), dried over Na2SO4, and evaporated to yield a yellow oil. This material was applied to a silica column and eluted using a gradient of 1:3 ? 2:3 EtOAc/hexane to yield compound 3 as a light yellow oil that solidified upon storage (10.76 g, 24.4 mmol, 90%). Analytical data: Rf 0.15 (1:3 EtOAc/hexane); mp: 55-57 C; 1H NMR (300 MHz, CDCl3) delta 7.34-7.33 (m, 10H), 5.48 (br d, 1H, J = 7.9 Hz), 5.15 (s, 2H), 5.09 (s, 2H), 4.43-4.36 (m, 1H), 4.15 (q, 2H, J = 7.1 Hz), 3.35 (s, 1H), 2.63-2.50 (m, 1H), 2.22-2.15 (m, 1H), 2.00-1.88 (m, 1H), 1.24 (t, 3H, J = 7.1 Hz); 13C NMR (75 MHz, CDCl3) delta 201.5, 171.7, 167.0, 156.0, 136.2, 135.2, 128.7, 128.5, 128.4, 128.2, 128.1, 67.4, 67.1, 61.4, 53.2, 49.2, 38.6, 26.2, 14.1. HRMS (ESI) Calcd for C24H27NO7Na [M+Na]+, 464.1685. Found 464.1673.
75.2%		Z-Glu-Obzl 3 (1.0 g, 2.7 mmol) was dissolved in dry THF (10 mL) at rt. Carbonyl diimidazole (0.48 g, 2.96 mmol) was added slowly and the mixture was then stirred for another 2 h. After the solution was cooled to 0 C., ethyl magnesium malonate solution 2 (4.7 mL, 1.2 mmol) was added, and the mixture was then stirred at rt overnight. The product was extracted with ester, and washed with 10% NaHCO3, water, and brine. After the solvent was evaporated, the residue was purified by flash chromatography on silica gel (Hexanes:EtOAc=1:1) and afford a white solid (0.9 g, 2.03 mmol, 75.2%). 1H NMR (400 MHz, CDCl3, 25 C.) delta 1.23 (t, 3H), 1.90-2.00 (m, 1H), 2.10-2.30 (m, 1H), 2.50-2.70 (m, 2H), 3.36 (s, 2H), 4.16 (q, 2H), 4.30-4.50 (m, 1H), 5.10 (s, 2H), 5.12 (s, 2H) 5.36 (m, 1H), 7.25-7.40 (m, 10H).

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 2698 - 2705
[2]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 553 - 559
[3]Patent: US2015/369800,2015,A1 .Location in patent: Paragraph 0167; 0169
[4]Tetrahedron Letters,2003,vol. 44,p. 7011 - 7013
[5]Angewandte Chemie - International Edition,2004,vol. 43,p. 3432 - 3436
[6]Journal of the American Chemical Society,2006,vol. 128,p. 8738 - 8739
[7]Journal of the American Chemical Society,2011,vol. 133,p. 3708 - 3711

33
[ 3705-42-8 ]
[ 175854-39-4 ]
[ 745062-96-8 ]

Reference： [1]Synthetic Communications,2004,vol. 34,p. 2077 - 2084

34
[ 855527-18-3 ]
[ 3705-42-8 ]
[ 855527-19-4 ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 7799 - 7809

35
[ 3705-42-8 ]
[ 167319-89-3 ]

Yield	Reaction Conditions	Operation in experiment
1.76 g		To a solution of L-glutamic acid (5.0 g, 34.0 mmol) in saturated NaHCO3 aq. (113 mL)was added CbzCl (7.3 mL, 51.0 mmol) at 0oC and then the mixture was stirred for 2 h at room temperature. The reaction mixture was added to Et2O and 1M HCl and extracted with AcOEt. The organic layer was washed with H2O and brine, dried over MgSO4, and evaporated under reduced pressure to give crude Cbz-Glu-OH as a white solid. To the residue was added Ac2O (30 mL) at 0oC and then the mixture was stirred for over night at room temperature. The reaction mixture was evaporated under reduced pressure to give crude N-benzyloxycarbonyl glutamic anhydride as an oil. To the residue in toluene(153 mL) was added BnOH (4.8 mL, 46.2 mmol) at room temperature and then the mixture was heated to reflux. After the stirring for 8 h, saturated NaHCO3 aq. was added to the reaction mixture and the resulting solution was washed with Et2O. The aqueous phase is acidified to pH 1 with 1M HCl and extracted with AcOEt. The organic phase was washed with H2O, brine, dried over MgSO4 and evaporated under reduced pressure to give crude product (8.91 g) as red oil. To the crude product (2.40 g, 6.5 mmol)in THF (65 mL) were added EtOCOCl (1.9 mL, 19.5 mmol) and Et3N (2.7 mL, 19.5mmol) at -15oC. After the stirring for 2 h, NaBH4 (733 mg, 19.5 mmol) and H2O (223mL) were added to the solution at same temperature. The reaction mixture was stirred for 2 h and then neutralized with 1M KHSO4. The organic solvents were evaporated and the product was extracted with AcOEt. The organic phase was washed with H2O and brine, dried over MgSO4, and the solvent was evaporated. The residue was purified by column chromatography (Hexane:AcOEt = 2:1~1:1) to afford 7 (rotamer ratio = 3:1)(1.76 g, 4.9 mmol, 53%, 4 steps) as a white solid.

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 7307 - 7314
[2]Chemical Communications,2011,vol. 47,p. 10915 - 10917
[3]Journal of Organic Chemistry,1998,vol. 63,p. 8432 - 8439
[4]Chemistry Letters,1996,p. 621 - 622
[5]Synthesis,2008,p. 2432 - 2438
[6]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2651 - 2655
[7]Tetrahedron Letters,2017,vol. 58,p. 1604 - 1606

36
[ 3705-42-8 ]
[ 60022-62-0 ]
[ 359868-56-7 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 2507 - 2510

37
[ 3705-42-8 ]
[ 4083-64-1 ]
[ 926623-04-3 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 787 - 789

38
[ 3705-42-8 ]
L-2-((7-hydroxycoumarin-4-yl)-ethane-2-yl)glycine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 8738 - 8739
[2]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 553 - 559

39
[ 3705-42-8 ]
(S)-2-((S)-3-Amino-3-carboxy-propyl)-4,5-dihydro-oxazole-4-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 2507 - 2510

40
[ 3705-42-8 ]
[ 173724-40-8 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

41
[ 3705-42-8 ]
(S)-2-Amino-5-oxo-5-trifluoromethanesulfonylamino-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

42
[ 3705-42-8 ]
[ 1053732-05-0 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

43
[ 3705-42-8 ]
(S)-2-{4-[(2,7-Dimethyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-2-fluoro-benzoylamino}-5-methanesulfonylamino-5-oxo-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

44
[ 3705-42-8 ]
(S)-2-{4-[(2,7-Dimethyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-2-fluoro-benzoylamino}-5-oxo-5-trifluoromethanesulfonylamino-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

45
[ 3705-42-8 ]
(S)-2-{4-[(2,7-Dimethyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-2-fluoro-benzoylamino}-5-oxo-5-(toluene-4-sulfonylamino)-pentanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

46
[ 3705-42-8 ]
[ 247904-31-0 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

47
[ 3705-42-8 ]
[ 1054635-48-1 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

48
[ 3705-42-8 ]
[ 1053267-68-7 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 3809 - 3820

49
[ 3705-42-8 ]
[ 2757-90-6 ]

Reference： [1]Helvetica Chimica Acta,1987,vol. 70,p. 1261 - 1267
[2]Journal of Organic Chemistry,1979,vol. 44,p. 3752 - 3755

50
[ 3705-42-8 ]
[ 4821-79-8 ]

Reference： [1]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 2796 - 2801
[2]Journal of medicinal chemistry,1966,vol. 9,p. 84 - 88

51
[ 3705-42-8 ]
[ 83789-61-1 ]

Reference： [1]Journal of the American Chemical Society,1989,vol. 111,p. 1436 - 1445

52
[ 3705-42-8 ]
[ 72669-53-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 62 percent / Et₃N / tetrahydrofuran; dimethylformamide / -5 deg C, 1 h, RT, 4 h 2: 68 percent / H₂ / 10percent Pd-C / aq. acetic acid / 4 h

Reference： [1]Sekine; Itakura; Namihisa; Takahashi; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 11, p. 3286 - 3289]

53
[ 3705-42-8 ]
[ 4311-12-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (i) nBu₃N, ClCO₂Et, (ii) /BRN= 605259/ 2: H₂ / Pd

Reference： [1]Larsen,P.O. [Acta Chemica Scandinavica (1947), 1965, vol. 19, p. 1071 - 1078]

54
[ 3705-42-8 ]
[ 2419-56-9 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1964,vol. 673,p. 196 - 207

55
[ 3705-42-8 ]
[ 74221-51-5 ]
[ 936478-00-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 48h;	Boc-Val-OH (8.69 g, 40.0, mmol) and Gly-OBzl'HCl (8.07 g, 40.0 mmol) were dissolved in methylene chloride (100 ml), and the solution was kept at 00C. Triethylamine (6.13 ml, 44.0 mmol), HOBt ( 1-hydroxybenzotriazole, 6.74 g, 44.0 mmol), and WSC-HCl (l-ethyl-3- ( 3- dimethylaminopropyl) carbodiimide hydrochloride, 8.44 g, 44.0 mmol) were added to the solution, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (200 ml). The solution was washed with water (50 ml), 5% citric acid aqueous solution (50 ml x twice), saturated brine (50 ml), 5% sodium hydrogencarbonate aqueous solution (50 ml x twice), and saturated brine (50 ml). The organic layer was dried over anhydrous magnesium sulfate, magnesium sulfate was removed by filtration, and the filtrate was <n="22"/>concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to obtain Boc- Val-Gly-OBzl (13.2 g, 36.2 ramol) as white crystals.Boc-Val-Gly-OBzl (5.47 g, 15.0 ?unol) was added to 4 N HCl/dioxane solution (40 ml), and the mixture was stirred at room temperature for 50 minutes. Dioxane was removed by concentration under reduced pressure, n-hexane (30 ml) was added to the residue, and- the mixture was concentrated under reduced pressure. This procedure was repeated 3 times to quantitatively obtain H-Val-Gly-OBzl»HCl .The above H-Val-Gly-OBzl »HC1 and Z-GIu-OBzI (5.57 g, 15.0 mmol) were dissolved in methylene chloride (50 ml), and the solution was kept at 00C. Triethylamine (2.30 ml, 16.5 mmol), HOBt (1-hydroxybenzotriazole, 2.53 g, 16.5 mmol), 'and WSC-HCl ( l-ethyl-3- ( 3- dimethylaminopropyl) carbodiimide hydrochloride, 3.16 g, 16.5 mmol) were added to the solution, and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in heated ethyl acetate (1500 ml). The solution was washed with water (200 ml), 5% citric acid aqueous solution (200 ml x twice), saturated brine (150 ml), 5% sodium hydrogencarbonate aqueous solution (200 ml x twice), and saturated brine (150 ml). The organic layer was dried -over anhydrous magnesium sulfate, magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The deposited crystals were collected by filtration, and dried under reduced pressure to obtain Z-GIu(VaI-GIy-OBzI)-OBzI (6.51 g, 10.5 mmol) as white crystals.The above Z-GIu(VaI-GIy-OBzI)-OBzI (6.20 g, 10.03 mmol) was suspended in ethanol (200 ml), and added with 10% palladium/carbon (1.50 g) , and reduction reaction was performed at 55C for 5 hours under a hydrogen atmosphere. During the reaction, 100 ml in total of water was gradually added. The catalyst was removed by filtration using a Kiriyama funnel, and the filtrate was concentrated under <n="23"/>reduced pressure to a half volume. The reaction mixture was further filtered through a membrane filter, and the filtrate was concentrated under reduced pressure. The residue was dissolved in a small volume of water, and added with ethanol to deposit crystals, and the crystals were collected by filtration, and dried under reduced pressure to obtain white powder of gamma-Glu-Val-Gly (2.85 g, 9.40 mmol) . ESI-MS: (M+H)+ = 304.11H-NMR (400 MHz, D2O) delta (ppm) : 0.87 (3H, d, J=6.8 Hz), 0.88 (3H, d, J=6.8 Hz), 1.99-2.09 (3H, m) , 2.38-2.51 (2H, m) 3.72 (IH, t, J=6.35 Hz), 3.86 (IH, d, J=17.8 Hz), 3.80 (IH, d, J=17.8 Hz), 4.07 (IH, d, J=6.8 Hz)
6.51 g	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 48h;	Then, H-Val-Gly-OBzl.HC1 and Z-Glu-OBzl (5.57 g, 15.0mmol) were dissolved in methylene chloride (50 ml), and thesolution was kept at 0 C. Triethylamine (2.30 ml, 16.5mmol), HOBt (1-hydroxybenzotriazole, 2.53 g, 16.5 mmol),and WSC.HC1 (1 -ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, 3.16 g, 16.5 mmol) were added to thesolution, and the mixture was stirred at room temperature for2 days. The reaction mixture was concentrated under reducedpressure, and the residue was dissolved in heated ethyl acetate(1500 ml). The solution was washed with water (200 ml), 5%citric acid aqueous solution (200 mlx twice), saturated brine(150 ml), 5% sodium hydrogencarbonate aqueous solution(200 mlx twice), and saturated brine (150 ml). The organiclayer was dried over anhydrous magnesium sulfate, then themagnesium sulfate was removed by filtration, and the filtratewas concentrated under reduced pressure. The depositedcrystals were collected by filtration, and dried under reducedpressure to obtain white crystals of Z-Glu(Val-Gly-OBzl)OBzl (6.51 g, 10.5 mmol).

Reference： [1]Patent: WO2007/55388,2007,A2 .Location in patent: Page/Page column 19-21
[2]Chemical and Pharmaceutical Bulletin,2016,vol. 64,p. 1181 - 1189
[3]Patent: US9395376,2016,B2 .Location in patent: Page/Page column 12

56
[ 1087223-92-4 ]
[ 3705-42-8 ]
C₈₃H₁₄₇N₃O₁₉ [ No CAS ]

Reference： [1]Tetrahedron,2009,vol. 65,p. 1455 - 1460

57
[ 3705-42-8 ]
[ 122760-31-0 ]
[ 1195771-40-4 ]

Reference： [1]Chemical Communications,2009,p. 821 - 823

58
[ 3705-42-8 ]
[ 34288-06-7 ]
[ 1245795-18-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4582 - 4586
[2]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

59
[ 3705-42-8 ]
[ 52068-30-1 ]
N-(benzyloxycarbonyl)-L-glutamic acid 1-(benzyl ester) 5-[(4-benzyloxy-phenyl)-hydrazide] [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4582 - 4586

60
[ 3705-42-8 ]
(3-(benzyloxy)phenyl)hydrazine hydrochloride [ No CAS ]
[ 1245795-19-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4582 - 4586

61
[ 3705-42-8 ]
[ 88-23-3 ]
C₂₆H₂₅ClN₂O₉S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		(Synthetic Example 10); Synthesis of N5-(2-hydroxy-3-sulfophenyl) -L-glutamine (Compound No. 10) <strong>[3705-42-8]Z-Glu-OBn</strong> (371mg, 1mmol) was dissolved in methylene chloride (1mL), and CDI (180mg, 1.1mmol) was added thereto and stirred at room temperature for 30 minutes. Then, 2-amino-4-chlorophenol-6-sulfonic acid (223mg, 1mmol) and THF (1mL) were added thereto and stirred overnight at room temperature. After removing a solvent, purification was conducted in accordance with the purification process A. The obtained intermediate was dissolved in a mixed solvent of methanol and water. Pd/C in catalyst quantity was added thereto and stirred under hydrogen atmosphere overnight at room temperature. After filtering out the catalyst and removing a solvent, purification was conducted in accordance with the purification process A to obtain a title compound. Yield amount: 120 mg (0.40mmol) yield: 40% 1H-NMR (D2O, 300MHz) : delta 7.67 (d, 1H, J=7.9Hz), 7.62 (d, 1H, J=8.2Hz), 7.07 (dd, 1H, J=7.9Hz, 8.2Hz), 3.92-3.97 (m, 1H), 2.59-2.64 (m, 2H), 2.25-2.20 (m, 2H) ESI(m/z) : 303[M+H]+

Reference： [1]Patent: EP2345636,2011,A1 .Location in patent: Page/Page column 17

62
[ 1155-62-0 ]
[ 100-51-6 ]
[ 3705-42-8 ]

Reference： [1]ChemBioChem,2012,vol. 13,p. 1319 - 1326

63
[ 3705-42-8 ]
[ 80-79-5 ]
[ 1336933-85-7 ]

Yield	Reaction Conditions	Operation in experiment
		(REFERENCE SYNTHESIS EXAMPLE 10) Synthesis of N5-(2-hydroxy-3-sulfophenyl)-L-glutamine (Reference Compound No. 10) [0122] methylene chloride (1 ml), and CDI (180 mg, 1.1 mmol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. 2-Amino-4-chlorophenol-6-sulfonic acid (223 mg, 1 mmol) and THF (1 ml) were added to the mixture. The mixture was then stirred overnight at room temperature. After the solvent was removed by distillation, the mixture was purified in accordance with the purification step A. The resulting intermediate was dissolved in a methanol-water solvent mixture. A catalytic amount of Pd/C was added to the solution. The mixture was stirred overnight at room temperature in a hydrogen atmosphere. After the catalyst was filtered off, the solvent was removed by distillation. The mixture was purified according to the purification step A to give the title compound.Yield amount: 120 mg (0.40 mmol), yield: 40%1H-NMR (D2O, 300MHz): delta 7.67 (d, 1H, J=7.9Hz), 7.62 (d, 1H, J=8.2Hz), 7.07 (dd, 1H, J=7.9Hz, 8.2Hz), 3.92-3.97 (m, 1H), 2.59-2.64 (m, 2H), 2.25-2.20 (m, 2H)ESI (m/z): 303 [M+H]+

Reference： [1]Patent: EP2551262,2013,A1 .Location in patent: Paragraph 0122

64
[ 3705-42-8 ]
[ 80-79-5 ]
C₂₆H₂₆N₂O₉S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		<strong>[3705-42-8]Z-Glu-OBn</strong> (371 mg, 1 mmol) was dissolved in methylene chloride (1 ml), and CDI (180 mg, 1.1 mmol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. 2-Amino-4-chlorophenol-6-sulfonic acid (223 mg, 1 mmol) and THF (1 ml) were added to the mixture. The mixture was then stirred overnight at room temperature. After the solvent was removed by distillation, the mixture was purified in accordance with the purification step A. The resulting intermediate was dissolved in a methanol-water solvent mixture. A catalytic amount of Pd/C was added to the solution. The mixture was stirred overnight at room temperature in a hydrogen atmosphere. After the catalyst was filtered off, the solvent was removed by distillation. The mixture was purified according to the purification step A to give the title compound. Yield amount: 120 mg (0.40 mmol), yield: 40%1H-NMR (D2O, 300 MHz): delta 7.67 (d, 1H, J=7.9Hz), 7.62 (d, 1H, J=8.2Hz), 7.07 (dd, 1H, J=7.9Hz, 8.2Hz), 3.92-3.97 (m, 1H), 2.59-2.64 (m, 2H), 2.25-2.20 (m, 2H)ESI (m/z): 303 [M+H]+

Reference： [1]Patent: EP2554165,2013,A1 .Location in patent: Paragraph 0096

65
(N-phenyl)-2,2,2-trifluoroacetimido-5-triisopropylsilyl-2,3-O-benzyl-α,β-D-ribofuranose [ No CAS ]
[ 3705-42-8 ]
[ 1430197-72-0 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 2306 - 2309

66
[ 3705-42-8 ]
2-(diphenylphosphanyl)-4-fluorophenol [ No CAS ]
[ 1461715-83-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere;	General procedure: A solution of the o-diphenylphosphinophenol (7, 1 equiv.), the commercially available N-carbobenzyloxy-L-aminoacid-1-benzyl ester (Z-Asp-OBn or <strong>[3705-42-8]Z-Glu-OBn</strong>, 1.2 equiv.) and N,N-dimethylaminopyridine (0.1 equiv.) in dry CH2Cl2 (0.1 M) were added, at room temperature andunder nitrogen, to a suspension of N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (EDC, 1.4 equiv.) and dry N,N-diisopropylethylamine (1.4 equiv.) in dry CH2Cl2. The mixture was stirred at RT for 2 h, monitoring by TLC (60:40 hexane/AcOEt). The reaction mixture was diluted with CH2Cl2 and washed with 5% aqueous HCl and water: the organic layer was dried over Na2SO4 and concentrated. The crude product obtained was purified by flash chromatography, as indicated in each case.

Reference： [1]Molecules,2013,vol. 18,p. 8779 - 8785

67
[ 3705-42-8 ]
L-Desmethylphosphinothricin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		DMPT was synthesized according to a procedure developed by AsisChem Inc. (Watertown, MA) with some modifications [15]. To 14.8 g (0.04 mol) Z-L-glutamic acid alpha-benzyl ester (Chem-Impex,Wood Dale, IL) 50 mL benzene, 0.4 g copper acetate, and 224 muL pyridine were added. The mixture was stirred at 20 C for 1 h, then 50 mL benzene and 8.8 g (0.027 mol) lead acetate were added. The reaction was refluxed under argon for 24 h, filtered through a celite pad, and rinsed with ethyl acetate (3× 20mL). The bright turquoise filtrate was washed with water (3 × 100 mL) and brine (3 × 100 mL), and the resulting yellow/brown organic layer was dried over 4 g anhydrous sodium sulfate. The product was purified by column chromatography over silicagel (ethyl acetate:hexanes, 1:9). Fractions containing the desired product were combined and concentrated by rotary evaporation.To the resulting yellow syrup 2 mL methanol, 8 mL 50% aqueous hypophosphorus acid, and 0.16 g 2,2?-azobis(2-methylpropionitrile) were added. The reaction was stirred at 75 C for 9 h. 30 mL water was added and the pH was adjusted to ~8 with saturated sodium carbonate. This mixture was washed with methyl tert-butylether (2 × 40 mL). The aqueous layer was adjusted to pH ~2 with 6 M hydrochloric acid. The desired product was extracted with dichloromethane(2 × 30 mL) and dried over anhydrous sodium sulfate. After concentration via rotary evaporation, 15 mL 6 M hydrochloric acidwas added and the reaction was refluxed under argon for 3 h. The resulting DMPT product was concentrated using rotary evaporation, and the yellow gel was resuspended in 3 mL water. DMPT was purified using cation exchange resin (Dowex AG-50, Acros Organics). The resin was washed stepwise with water followed by 10mM sodium carbonate at pH 8, 9, and 10. DMPT was eluted with 10 mM sodium carbonate, pH 11. The eluant was concentrated via rotary evaporation, and the resulting yellow oil was transferred into the anaerobic chamber to deaerate. The concentration of DMPT was determined by 31P nuclearmagnetic resonance (NMR) spectroscopy by comparison with a phosphonate standard of known concentration. DMPT was resuspended in 1 M K+ EPPS, pH 8 at a concentration of 80-100 mM and stored in aliquotsat -80 C.

Reference： [1]Biochimica et Biophysica Acta - Proteins and Proteomics,2014,vol. 1844,p. 2135 - 2144

68
[ 872100-85-1 ]
[ 3705-42-8 ]
benzyl N²-[(benzyloxy)carbonyl]-N⁵-[2-({α-D-mannopyranosyl-(1→3)-[α-D-mannopyranosyl-(1→6)]-α-D-mannopyranosyl}oxy)ethyl]-L-glutaminate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In water; N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of 2-aminoethyl alpha-D-mannopyranosyl-(1?3)-[alpha-D-mannopyranosyl-(1?6)]-alpha-D-mannopyranoside (2.6 g, 4.75 mmol), and (S)-5-(benzyloxy)-4-[(benzyloxy)carbonyl]amino}-5-oxopentanoic acid (2.0 g, 5.39 mmol) in DMF (36 mL) at 0 C. was added DMAP (580 mg, 4.75 mmol) and EDC (3.64 g, 19.00 mmol). The reaction mixture was allowed to gradually warm up to rt. After stirring for 16 hr, the reaction mixture was concentrated and the residue was purified by flash chromatography on C18 reverse phase silica gel (275 g), eluting with 10-55% AcCN in H2O to give the title compound. UPLC Method B: calculated for C40H56N2O21 900.34, observed m/e: 901.26 [M+1]; Rt=2.46 min.
	With dmap; 1,2-dichloro-ethane; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;	To a solution of 2-aminoethyl alpha-D-mannopyranosyl-(1?3)-[alpha-D-mannopyranosyl- (1?6)]-alpha-D-mannopyranoside (2.6 g, 4.75 mmol), and (S)-5-(benzyloxy)-4- [(benzyloxy)carbonyl]amino}-5-oxopentanoic acid (2.0 g, 5.39mmol) in DMF (36 mL) at 0 C was added DMAP (580 mg, 4.75 mmol) and EDC (3.64 g, 19.00 mmol). The reaction mixture was allowed to gradually warm up to rt. After stirring for 16 hr, the reaction mixture was concentrated and the residue was purified by flash chromatography on C18 reverse phase silica gel (275g), eluting with 10-55% AcCN in H2O to give the title compound. UPLC Method B: calculated for C40H56N2O21 900.34, observed m/e: 901.26 [M+1]; Rt = 2.46 min.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;	To a mixture of 2-aminoethyl alpha-D-mannopyranosyl-(1?3)-[alpha-D- mannopyranosyl-(1?6)]-alpha-D-mannopyranoside (4.0 g, 7.31 mmol) and (S)-5-(benzyloxy)-4- [(benzyloxy)carbonyl]amino}-5-oxopentanoic acid (2.98 g, 8.04 mmol) in DMF (30 mL) at rt was added EDC (2.10 g, 10.96 mmol) and HOBt (112 mg, 0.731 mmol). The mixture was allowed to stir at rt. After overnight, the reaction mixture was concentrated, and the residue was purified on C18 reverse phase cartridge on Biotage (0-65% AcCN in water). The desired fractions were combined and freeze-dried to give the title compound. UPLC-MS Method D: m/z = 901.01 (z = 1); tR = 4.04 min.

Reference： [1]Patent: US2015/105317,2015,A1 .Location in patent: Paragraph 0430
[2]Patent: WO2016/164288,2016,A1 .Location in patent: Page/Page column 108; 109
[3]Patent: WO2018/175272,2018,A1 .Location in patent: Page/Page column 204; 205

69
[ 68172-39-4 ]
[ 3705-42-8 ]
(2S,4R)-benzyl 1-((S)-5-(benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoyl)-4-hydroxypyrrolidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.5%		Et3N (390 muL) was added viasyringe to a solution containing Cbz-Glu-OBzl (1.0382 g, 2.80 mmol) and HBTU (1.0728 g, 2.83 mmol) in 5 mL of anhydrous DMF under Ar (g). The carboxylic acid of Cbz-Glu-OBzl was allowed to activated for 20 min at room temperature before being transferred via syringe to a solution of the hydroxyproline benzyl ester 12a (1.003 g, 2.55 mmol) and Et3N (354 muL) in 2 mL of anhydrous DMF under Ar (g). The solution was stirred at room temperature for 15 h. The crude mixture was extracted with EtOAc and washed sequentially with 10% HCl (50 mL), 10% NaHCO3 (50 mL), and brine (50 mL). The organic layer was dried over anhydrous Na2SO4 (s), and the solvent was removed in vacuo. The product was purified by silica flash chromatography (71:24:5 Hex:EtOAc:MeOH) to give a white solid in 76.5% yield. 1HNMR (300 MHz, CD3OD) delta: 1.844-2.432 (m, 6 H), 3.331-3.550 (m, 2 H),4.398-4.443 (m, 2 H), 4.592-4.647 (t, J = 8.1 Hz, 1 H), 5.031-5.210 (m,6 H), 5.780-5.807 (d, J = 8.1 Hz, 1 H), 7.277-7.375 (m, 15 H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 2536 - 2539

70
[ 3705-42-8 ]
(2R,4S)-4-hydroxyproline benzyl ester [ No CAS ]
(2R,4S)-benzyl 1-((S)-5-(benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoyl)-4-hydroxypyrrolidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.3%		Et3N(195 muL) was added via syringe to a solution containing Cbz-Glu-OBzl (0.5191 g,1.40 mmol) and HBTU (0.5308 g, 1.40 mmol) in 4 mL of anhydrous DMF under Ar(g). The carboxylic acid of Cbz-Glu-OBzl was allowed to activated for 20 min at room temperature before being transferred via syringe to a solution of the hydroxyproline benzyl ester 12b (0.4995 g, 1.27 mmol) and Et3N (177 muL) in 2 mL of anhydrous DMF under Ar (g). The solution was stirred at room temperature for 15 h. The crude mixture was extracted with EtOAc andwashed sequentially with 10% HCl (50 mL), 10% NaHCO3 (50 mL), andbrine (50 mL). The organic layer was dried over anhydrous Na2SO4(s), and the solvent was removed in vacuo. The product was purifiedby silica flash chromatography (71:24:5 Hex:EtOAc:MeOH) to give a white solidin 65.3% yield. 1H NMR (300 MHz, CDCl3) delta: 1.881-2.467(m, 10 H), 3.473-3.639 (m, 2 H), 3.741-3.947 (m, 1 H), 4.369-4.557 (m, 2 H),4.873-5.196 (m, 13 H), 5.999-6.025 (d, J = 7.8, 1 H), 6.100-6.126 (d, J= 7.8, 1 H), 7.305-7.323 (m, 30 H). 31P NMR (300 MHz, CDCl3)delta: 7.847, 7.922.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 2536 - 2539

71
[ 3705-42-8 ]
[ 6148-64-7 ]
[ 608535-19-9 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 4988 - 4992

72
[ 628-99-9 ]
[ 3705-42-8 ]
C₂₉H₃₉NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;Inert atmosphere;	The alpha-(n-benzyl)-L-glutamate-N-alpha-benzylcarbonyl acid (5 g, 1 equiv.), 2-nonanol (2.92 g, 1,5 equiv.), EDCI (2.58 g, 1 equiv.), HOBT (1.82 g, 1 equiv.) and DMAP (1.65 g, 1 equiv.) are suspended in dichloromethane (100 ml). The reaction medium is stirred at room temperature overnight. The medium is successively washed with a 0.1N hydrochloric acid solution, a saturated sodium hydrogencarbonate solution and then with a saturated sodium chloride solution. The organic phase is dried on magnesium sulphate, filtered and concentrated in order to lead to a pale yellow oil which is then purified by chromatography on silica gel (heptane:ethyl acetate gradient (100:0 to 50:50) in order to lead to a yellow oil (2.65 g, yield 40%) which will be reengaged into stage 2.
40%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;Inert atmosphere;	With magnetic stirring,A 250 ml one-necked flask placed under a nitrogen sweepAlpha- (n-benzyl) -L-glutamate-N-alpha-benzylcarbonylic acid(5 g, 1 eq),2-nonanol(2.92 g, 1.5 eq),EDCI(2.58 g, 1 eq),HOBT(1.82 g, 1 eq) andDMAP(1.65 g, 1 eq) was added toIt is suspended in dichloromethane (100 ml).The reaction medium is stirred overnight at room temperature.This medium0.1 N hydrochloric acid solution,Saturated sodium bicarbonate solution,Then,Wash sequentially with saturated sodium chloride solution.The organic phase was dried over magnesium sulfate,Filtered,Concentrate to give a pale yellow oil,It is then chromatographed on silica gel(From heptane: ethyl acetate gradient (100: 0 to 50: 50) to give a yellow oil (2.65 g, 40% yield)Place it again under Phase 2.

Reference： [1]Patent: US2016/60208,2016,A1 .Location in patent: Paragraph 0131
[2]Patent: JP2016/508974,2016,A .Location in patent: Paragraph 0070-0072

73
[ 6893-26-1 ]
[ 3705-42-8 ]
2R-(N-(S)-(4-(benzyloxycarbonyl)-(4-benzyloxycarbonylamino)-1-oxobutyl)amino)pentanedioic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.2 g		2R-(N-(S)-4-(Benzyloxycarbonyl)-4-benzyloxycarbonylamino)-1-oxobutyl)amino)pentanedioic acid. 20 (0346) To a 250 mL flask (magnetic stirrer, addition funnel and N2 inlet) was charged D-Glutamic acid (10.9 g, 74.1 mmol) and THF (110 mL). Stirring was started as N,O-bis(trimethylsilyl) acetamide (53.1 g, 261 mmol) was added over 5 minutes using the addition funnel. This slurry was stirred for 28 hours at ambient temperature. (0347) To a second 250 mL flask (magnetic stirrer, thermocouple, charging port and N2 inlet) was charged N-benzyloxycarbonyl-L-glutamate-alpha-benzyl ester (25.0 g, 67.3 mmol) and THF (80 mL) and stirred to obtain a homogeneous solution. The solution was cooled to -25±5 C. and N-methylmorpholine (8.28 g, 81.8 mmol) was added by syringe and the solution stirred at that temperature for about 30 minutes. The 1 L main reaction flask (mechanical stirrer, thermocouple, charging port and N2 inlet) was charged with THF (170 mL) and the THF cooled to -30±5 C. At this point isobutyl chloroformate (10.0 g, 73.2 mmol) was charged and then the N-benzyloxycarbonyl-L-glutamate-alpha-benzyl ester N-methylmorpholine salt was transferred to the main reaction flask using a piston pump and Teflon tubing at a rate of approximately 2.0 mL/min keeping the temperature of the reaction mixture at -30±5 C. After 45 minutes transfer was complete. The reaction mixture was stirred at -30±5 C. for about 40 minutes (the mixed anhydride/symmetrical anhydride ratio was 95.5/0.28) and then the persilylated D-glutamate ester solution was transferred to the mixed anhydride solution using the pump over 35 minutes keeping the temperature at -30±5 C. during the transfer. The reaction mixture was stirred at this temperature range for 1 hour then slowly allowed to warm to ambient temperature and stirred overnight. (0348) The reaction was carefully quenched by addition of water (75 mL), diluted with EtOAc (200 mL), then acidified to a pH of 1-2 with 37% HCl (1.6 g). The organic phase was washed with water (2×50 mL), 20% brine (2×50 mL) and the organic phase reduced in volume in vacuo to a volume of 112 mL. The product solution was diluted with MeCN (285 mL), transferred to the reaction flask and the solution distilled at atmospheric pressure, collecting 310 mL of distillate. The residue was diluted with 0.2% ?water wet? MeCN (456 mL) and heated to reflux to obtain a homogeneous solution. The solution was slowly cooled to ambient temperature and the resulting thick slurry stirred overnight. The solids were collected by filtration, the cake washed with MeCN (45 mL) and the filtrates drawn out under vacuum. The cake was then dried to constant weight under a stream of nitrogen. Yield: 29.2 g (86.8%) Purity: 99.1 A %. C,H,N analysis: Theory; C, 59.99%; H, 5.64%; N, 5.60%. Found: C, 59.96%; H, 5.48%; N, 5.51%

Reference： [1]Patent: US9458188,2016,B2 .Location in patent: Page/Page column 40

74
[ 57260-73-8 ]
[ 6367-08-4 ]
[ 3705-42-8 ]
[ 76-05-1 ]
benzyl (2S)-5-({(5S)-5-acetamido-6-[(2-aminoethyl)amino]-6-oxohexyl}amino)-2-[(benzyloxy)carbonyl] amino}-5-oxopentanoate trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The title compound was synthesized with classical methods of peptide chemistry starting with coupling of tert-butyl (2-aminoethyl)carbamate with intermediate L3 with HATU and N,Ndiisopropylethylamine, removal of the Z-protecting group by hydrogenation in DCM/methanol 1:1 over 10% palladiumlactivated charcoal under normal pressure, coupling of the obtained intermediate with (4S)-5-(benzyloxy)-4- { [(benzyloxy)carbonyl]amino } -5 -oxopentanoic acid with HATU and N,N10 diisopropylethylamine and finally removal of the Boc-protecting group by stiring for I h in a 25%solution of trifluoro acetic acid in dichloromethane.LC-MS (Method 1): R1 = 0.66 mm; MS (ESIpos): mz = 584 (M+H)t.

Reference： [1]Patent: WO2016/207090,2016,A2 .Location in patent: Page/Page column 284

75
[ 6367-08-4 ]
[ 3705-42-8 ]
N⁶-L-gamma-glutamyl-N²-acetyl-N-[2-({(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]butanoyl}amirto)ethyl]-L-lysinamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: palladium 10% on activated carbon; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane; methanol / 1 h 2.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide 2.2: 2 h / 50 °C

Reference： [1]Current Patent Assignee: BAYER AG - WO2016/207090, 2016, A2

76
[ 3705-42-8 ]
[3-ethoxy-3-hydroxyacrylato^(2-)-O¹O³]magnesate⁽²⁺⁾ [ No CAS ]
[ 608535-19-9 ]

Reference： [1]Organic Letters,2017,vol. 19,p. 2797 - 2800

77
[ 3705-42-8 ]
[ 637-04-7 ]
C₂₇H₂₉N₃O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

78
[ 3705-42-8 ]
[ 2924-16-5 ]
C₂₆H₂₆FN₃O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

79
[ 3705-42-8 ]
[ 60480-83-3 ]
C₂₈H₃₁N₃O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

80
(2-fluoro-4-(methylsulfonyl)phenyl)hydrazine [ No CAS ]
[ 3705-42-8 ]
benzyl N2-((benzyloxy)carbonyl)-N5-((2-fluoro-4-(methylsulfonyl)phenyl)amino)-L-glutaminate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-ethyl-N,N-diisopropylamine; O?(1H?benzotriazol?1?yl)?N,N,N?,N??tetramethyluronium tetrafluoroborate; In N,N-dimethyl-formamide; at -25 - 20℃;	To a solution of 1-benzyl N-carbobenzoxy-L-glutamate 13 (200 mg, 0.539 mmol), (2-fluoro-4-(methylsulfonyl)phenyl)hydrazine 10b (131.97 mg, 0.646 mmol, 1.2 equiv) and TBTU (259.38 mg, 0.808 mmol, 1.5 equiv) in DMF (2 mL) cooled to -25c was added DIPEA (0.329 mL, 1.885 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was then poured into brine (50 mL) and extracted with EtOAc (3 X 50 mL). The organic layer was washed consecutively with 1M aqueous KHSO4 (50 mL), aqueous NaHCO3 (50 mL), and brine solution (50 mL). After drying (Na2SO4), the solvent was evaporated under reduced pressure. The crude product was purified through column chromatography, eluting with ethyl acetate in n-hexane to give benzyl N2-((benzyloxy)carbonyl)-N5-((2-fluoro-4-(methylsulfonyl)phenyl)amino)-L-glutaminate as a white solid 11b (255 mg, 85%). 1H NMR (300 MHz, DMSO-d6): delta 9.90 (s, 1H), 8.52 (s, 1H), 7.85 (d, J = 7.81 Hz, 1H), 7.59 (dd, J = 11.14, 1.43 Hz, 1H), 7.47 (d, J = 8.38 Hz, 1H), 7.42 -7.25 (m, 10H), 6.83 (t, J = 8.38 Hz, 1H), 5.15 (s, 2H), 5.10 - 5.03 (m, 2H), 4.20 - 4.08 (m, 1H), 3.13 (s, 3H), 2.34 (t, J = 7.38 Hz, 2H), 2.16 - 1.98 (m, 1H), 1.92 - 1.75 (m, 1H); LC-MS (m/z): 558.1 [M+H]+.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 529 - 532

81
[ 3705-42-8 ]
6-amino-N-(2-[α-D-mannopyranosyl-(1→3)-[α-D-mannopyranosyl-(1→6)]-α-D-mannopyranosyl]oxy}ethyl)hexanamide [ No CAS ]
benzyl N²-[(benzyloxy)carbonyl]-N⁵-(6-oxo-6-[2-({α-D-mannopyranosyl-(1→3)-[α-D-mannopyranosyl-(1→6)]-α-D-mannopyranosyl}oxy)ethyl]amino}hexyl)-L-glutaminate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;	To a solution of 6-amino-N-[2-({alpha-D-mannopyranosyl-(1?3)-[alpha-D- mannopyranosyl-(1?6)]-alpha-D-mannopyranosyl}oxy)ethyl]hexanamide (2.96 g, 4.48 mmol) and Z-GLU-OBZL (1.83 g, 4.93 mmol) in DMF (30 mL) was added EDC (1.288 g, 6.72 mmol) and HOBt (0.069 g, 0.448 mmol). The mixture was allowed to stir at rt overnight. After overnight, the reaction mixture was concentrated, and the residue was purified on 120 g C18 using Biotage (0-50% AcCN in water) to give the title compound. UPLC-MS Method D: m/z = 1014.49 (z = 1); tR = 4.26 min.

Reference： [1]Patent: WO2018/175272,2018,A1 .Location in patent: Page/Page column 206

82
[ 524-38-9 ]
[ 3705-42-8 ]
1-benzyl 5-(1,3-dioxoisoindolin-2-yl)-N-((benzyloxy)carbonyl)-L-glutamate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 774 - 779

83
[ 3705-42-8 ]
N-acetyl-L-alanyl-D-alanyl-N¹-{(2S)-1-[(2-aminoethyl)amino]-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-1-oxobutan-2-yl}-L-aspartamide [ No CAS ]
[ 79642-50-5 ]
N-acetyl-L-alanyl-D-alanyl-N¹-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-1-({2-[(N-{5-[(2,5-dioxopyrrolidin-1-yl)oxy]-5-oxopentanoyl}-L-gamma-glutamyl)amino]ethyl}amino)-1-oxobutan-2-yl]-L-aspartamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		N-Acetyl-L-alanyl-D-alanyl-N1-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-1-({2-[(N-{5-[(2,5-dioxopyrrolidin-1-yl)oxy]-5-oxopentanoyl}-L-gamma-glutamyl)amino]ethyl}amino)-1-oxobutan-2-yl]-L-aspartamide First of all, Intermediate C0112 was coupled to (4S)-5-(benzyloxy)-4-[(benzyloxy)carbonyl]amino}-5-oxopentanoic acid in the presence of HATU and N,N-diisopropylethylamine. This was followed by complete deprotection by hydrogenation over 10% palladium on activated carbon in DCM/methanol 1:1 at RT under hydrogen standard pressure for 1 hour. Finally, the title compound was obtained by reaction with 5 equivalents of 1,1'-[(1,5-dioxopentane-1,5-diyl)bis(oxy)]dipyrrolidine-2,5-dione in DMF in the presence of 3 equivalents of N,N-diisopropylethylamine. LC-MS (Method 1): Rt=0.91 min; MS (ESIpos): m/z=1194 [M+H]+.

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2565-2567

84
[ 756525-95-8 ]
[ 3705-42-8 ]
C₃₁H₄₂N₂O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49.4%	With 1-hydroxy-7-aza-benzotriazole; triethylamine; HATU; In dichloromethane; at 20℃;	To a solution of Z-Glu-OBz (0.5 g, 1.356 mmol) in CH2CI2 (3 mL) was added amino-DPEG2 t-buty ester (3 14 mg, 1.35 mmol), HATU (614 mg, 1.62 mmol), HO At (220 mg, 1 62 mmol) and TEA (0.563 ml, 4.04 mmol). The reaction mixture was stirred overnight at room temperature, diluted with EtOAc, and washed with brine (3x). The organic phase s dried over Na2S04, and concentrated. The crude product was purified on silica gel (ISCO, 40 g, 0-10 % MeOH / DCM eluent) to afford compound 74 (390 mg, 49.4 % yield). ESI MS: C31H42N2O9 (M+H) 587.3; found 587 3

Reference： [1]Patent: WO2019/126691,2019,A1 .Location in patent: Paragraph 01233

85
[ 3705-42-8 ]
[ 75-31-0 ]
[ 4311-12-0 ]

Yield	Reaction Conditions	Operation in experiment
62.6%	Stage #1: Cbz-(L)-Glu-OBn; isopropylamine With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; water at 20℃; for 10h;	1 Example 1 - Synthesis of Compound 101 Isopropylamine (0.28 mL, 3.2 mmol) was added to a solution of Z-Glu-OBzl (1.00 g, 2.7 mmol), PyBOP (2.80 g, 5.4 mmol) and N,N-diisopropylethylamine (1.41 mL, 8.1 mmol) in anhydrous dichloromethane (6 mL). The reaction mixture was yellow and stirred overnight at room temperature. Then the mixture was diluted with ethyl acetate and washed with water. The organic phase was dried over anhydrous Na2SCU, filtered and concentrated under the reduced pressure. Subsequently, the crude product was purified by column chromatography on silica gel (hexane/ethyl acetate 1/1, v/v) to afford a white solid (0.56 g, 50.5% yield).A mixture of the white solid from the prior step (0.56 g, 1.4 mmol) and 10% Pd/C (0.30 g, 2.8 mmol) in 10 mL tetrahydrofuran/PbO (1/1, v/v) was stirred under an atmosphere (balloon) at room temperature and monitored by TLC. After 10 h, the mixture was filtered through a membrane filter (0.45 pm). And the filtrate was concentrated in vacuo to give the corresponding crude product. In the next step, the crude product was dissolved in H2O, filtered through a membrane filter (0.22 pm) twice and lyophilized to afford the final pure Compound 101 as a white solid (0.16 g, 62.6% yield).

Reference： [1]Current Patent Assignee: Firmenich International SA - WO2021/209345, 2021, A1 Location in patent: Page/Page column 59

86
[ 488-43-7 ]
[ 3705-42-8 ]
benzyl (2S)-2-(benzyloxycarbonylamino)-5-oxo-5-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4 g	Stage #1: Cbz-(L)-Glu-OBn With 4‐(4,6dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: 1-Amino-1-deoxy-D-glucitol In N,N-dimethyl-formamide at 25℃; for 12h;	4 General procedure for preparation of benzyl (2S)-2-(benzyloxycarbonylamino)-5-oxo-5- [[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentanoate (1-12). General procedure: To a solution of compound 11A (6.03 g, 16.27 mmol, 1.1 eq) in N,N-dimethylformamide (27 mL) was added 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate (DMTMMT) (9.7 g, 29.59 mmol, 2 eq) and triethylamine (2.24 g, 22.19 mmol, 1.5 eq) successively. After stirred at 25 °C for 0.5 hr, compound 1-11 (2.68 g, 14.79 mmol, 1 eq) was added and the reaction mixture was stirred at 25 °C for 12 hrs. LCMS (retention time of product = 0.253) showed the starting material was consumed and new peak with desired MS was detected. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (6 x 50 mL). The combined organic layers were washed with brine (3 x 130 mL), dried over NaiSCL and filtered. The filtrate was concentrated under reduced pressure and the residue was high vacuumed to give an oil. The oil was purified by reverse phase HPLC (3 kg Agela Cl 8 column, CH3CN/H2O, 300 mL/min, gradient: 30% CH3CN for 10 min, 30% to 45% CH3CN in 30 min, 45% CH3CN for 35 min; about 15 grams of crude product was dissolved in 70 mL of DMF to load on the column) to afford product 1-12 (4 g, 6.74 mmol, yield 46.1%, purity 99%) as a white solid. 'H NMR (400 MHz, DMSO-d6) d 1.72 - 1.85 (m, 1 H) 1.91 - 2.03 (m, 1 H) 2.18 (br t, J=7.44 Hz, 2 H) 2.96 - 3.03 (m, 1 H) 3.24 (dt, J=13.16, 5.17 Hz, 2 H) 3.37 - 3.40 (m, 2 H) 3.44 (br s, 2 H) 4.04 - 4.11 (m, 1 H) 4.29 (d, J=6.38 Hz, 1 H) 4.39 - 4.45 (m, 2 H) 4.51 (d, J=5.63 Hz, 1 H) 4.75 (d, J=4.63 Hz, 1 H) 4.96 - 5.14 (m, 4 H) 7.19 - 7.46 (m, 10 H) 7.68 - 7.85 (m, 2 H).

Reference： [1]Current Patent Assignee: MEDIBOSTON - WO2021/173773, 2021, A1 Location in patent: Paragraph 000733-000734

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[ CAS No. 3705-42-8 ] {[proInfo.proName]}

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[ 3705-42-8 ] Synthesis Path-Upstream 1~15

[ 3705-42-8 ] Synthesis Path-Downstream 1~86

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Amino Acid

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