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【结 构 式】 
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【分子编号】37627 【品名】(8S,14S,17R,20S)-17-benzyl-14-[2-(tert-butoxy)-2-oxoethyl]-8-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-imino-20-isopropyl-1-(4-methoxyphenyl)-19-methyl-9,12,15,18-tetraoxo-1,1-diphenyl-2,4,10,13,16,19-hexaazahenicosan-21-oic acid 【CA登记号】 |
【 分 子 式 】C66H76N8O11 【 分 子 量 】1157.37676 【元素组成】C 68.49% H 6.62% N 9.68% O 15.21% |
合成路线1
该中间体在本合成路线中的序号：(X),(XI)Cilengitide is synthesized using solid-phase Merrifield-type methods by sequentially adding N-Boc-N-Me-L-Val (I), N-Boc-D-Phe (III), N-Boc-4-O-t-Bu-L-Asp (V), N-Boc-Gly (VII) and Nalpha-Fmoc-Nomega-Mtr-L-Arg (IX) in a stepwise manner to a 4-hydroxymethylphenoxymethyl-polystyrene resin (Wang type resin), yielding peptide-resin intermediates (II), (IV), (VI), (VIII) and (X), respectively. Elimination of the resin from the peptide chain with a 1:1 mixture of TFA/dichloromethane results in the linear peptide (XI), which is then deprotected at the amino-terminal group by removing the Fmoc group with a 1:1 mixture of piperidine/DMF, to give peptide (XII).
| 【1】 Graul, A.; Sorbera, L.A.; Castañer, J.; Cilengitide. Drugs Fut 2000, 25, 7, 674. |
| 【2】 Jonczyk, A.; Goodman, S.; Diefenbach, B.; Sutter, A.; Holzmann, G.; Kessler, H.; Dechantsreiter, M. (Merck Patent GmbH); Cyclic adhesion inhibitors. DE 19534177; EP 0770622; JP 1997132593; US 6001961 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I),(II) | 27154 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methylbutyric acid | 45170-31-8 | C11H21NO4 | 详情 | 详情 |
| (X),(XI) | 37627 | (8S,14S,17R,20S)-17-benzyl-14-[2-(tert-butoxy)-2-oxoethyl]-8-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-imino-20-isopropyl-1-(4-methoxyphenyl)-19-methyl-9,12,15,18-tetraoxo-1,1-diphenyl-2,4,10,13,16,19-hexaazahenicosan-21-oic acid | C66H76N8O11 | 详情 | 详情 | |
| (III) | 22184 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid | C14H19NO4 | 详情 | 详情 | |
| (IV) | 37622 | (2S)-2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl](methyl)amino]-3-methylbutyric acid | C20H30N2O5 | 详情 | 详情 | |
| (V) | 37623 | (2S)-4-(tert-butoxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid | C13H23NO6 | 详情 | 详情 | |
| (VI) | 37624 | (6S,9R,12S)-9-benzyl-6-[2-(tert-butoxy)-2-oxoethyl]-12-isopropyl-2,2,11-trimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid | C28H43N3O8 | 详情 | 详情 | |
| (VII) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (VIII) | 37625 | (9S,12R,15S)-12-benzyl-9-[2-(tert-butoxy)-2-oxoethyl]-15-isopropyl-2,2,14-trimethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-oic acid | C30H46N4O9 | 详情 | 详情 | |
| (IX) | 37626 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(4-methoxyphenyl)(diphenyl)methyl]amino]methyl)amino]pentanoic acid | C41H40N4O5 | 详情 | 详情 | |
| (XII) | 37628 | (8S,14S,17R,20S)-8-amino-17-benzyl-14-[2-(tert-butoxy)-2-oxoethyl]-3-imino-20-isopropyl-1-(4-methoxyphenyl)-19-methyl-9,12,15,18-tetraoxo-1,1-diphenyl-2,4,10,13,16,19-hexaazahenicosan-21-oic acid | C51H66N8O9 | 详情 | 详情 |