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【结 构 式】 
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【分子编号】18862 【品名】(5S,8S,11R,14S,17S)-19-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-4-(2-aminoethyl)-5-benzyl-8-[4-(tert-butoxy)benzyl]-14-[4-[(tert-butoxycarbonyl)amino]butyl]-1-(9H-fluoren-9-yl)-11-(1H-indol-3-ylmethyl)-17-isopropyl-3,6,9,12,15,18-hexaoxo-2-oxa-4,7,10,13,16,19-hexaazatricosan-23-oic acid 【CA登记号】 |
【 分 子 式 】C87H113N11O15 【 分 子 量 】1552.91936 【元素组成】C 67.29% H 7.33% N 9.92% O 15.45% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Compound (XVI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin. To the Thr-bound resin (XI) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc-Tyr(t-Bu)OH (XII), and Fmoc- (N-allyloxycarbonylaminoethyl)PheOH (XIV) to yield the corresponding peptide-bound resins (XIII) and (XV), respectively. Then, allyl and allyoxycarbonyl protecting groups were both removed from the linear peptide-bound resin (XV) by treatment with tetrakis(triphenylphosphine)palladium, acetic acid, and N-methylmorpholine (NMM) in chloroform to yield compound (XVI).
| 【1】 Gilon, C.; et al.; A backbone-cyclic, receptor 5-selective somatostatin analogue: Synthesis, bioactivity, and nuclear magnetic resonance conformational analysis. J Med Chem 1998, 41, 6, 919. |
| 【2】 Hornik, V.; Seri-Levy, A.; Gellerman, G.; Gilon, C. (Yissum Research Development Co.); Conformationally constrained backbone cyclized somatostatin analogs. WO 9804583 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 18857 | allyl (10S,13S)-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-10-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate | C51H76N8O10 | 详情 | 详情 | |
| (XII) | 18858 | (2S)-3-[4-(tert-butoxy)phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C28H29NO5 | 详情 | 详情 | |
| (XIII) | 18859 | allyl (10S,13S)-10-[[(2R)-2-([(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]amino)-3-(1H-indol-3-yl)propanoyl]amino]-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate | C64H93N9O12 | 详情 | 详情 | |
| (XIV) | 18860 | (2S)-2-[(2-[[(allyloxy)carbonyl]amino]ethyl)[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid | C30H30N2O6 | 详情 | 详情 | |
| (XV) | 18861 | allyl (10S,13S,16R,19S,22S)-24-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-10-benzyl-13-[4-(tert-butoxy)benzyl]-19-[4-[(tert-butoxycarbonyl)amino]butyl]-9-[(9H-fluoren-9-ylmethoxy)carbonyl]-16-(1H-indol-3-ylmethyl)-22-isopropyl-5,11,14,17,20,23-hexaoxo-4-oxa-6,9,12,15,18,21,24-heptaaza-1-octacosen-28-oate | C94H121N11O17 | 详情 | 详情 | |
| (XVI) | 18862 | (5S,8S,11R,14S,17S)-19-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-4-(2-aminoethyl)-5-benzyl-8-[4-(tert-butoxy)benzyl]-14-[4-[(tert-butoxycarbonyl)amino]butyl]-1-(9H-fluoren-9-yl)-11-(1H-indol-3-ylmethyl)-17-isopropyl-3,6,9,12,15,18-hexaoxo-2-oxa-4,7,10,13,16,19-hexaazatricosan-23-oic acid | C87H113N11O15 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)The cyclization between free amino and acid groups of compound (XVI) was effected by reaction with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (PyBOP) to give the cyclic peptide (XVII). Finally, treatment with moist trifluoroacetic acid (TFA) containing a trace of ethanedithiol (EDT) and triisopropylsilane (TIS) at 0 C removed all protecting groups and liberated from the resin the peptide amide, which was finally purified by reversed-phase preparative HPLC.
| 【1】 Gilon, C.; et al.; A backbone-cyclic, receptor 5-selective somatostatin analogue: Synthesis, bioactivity, and nuclear magnetic resonance conformational analysis. J Med Chem 1998, 41, 6, 919. |
| 【2】 Hornik, V.; Seri-Levy, A.; Gellerman, G.; Gilon, C. (Yissum Research Development Co.); Conformationally constrained backbone cyclized somatostatin analogs. WO 9804583 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 18862 | (5S,8S,11R,14S,17S)-19-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-4-(2-aminoethyl)-5-benzyl-8-[4-(tert-butoxy)benzyl]-14-[4-[(tert-butoxycarbonyl)amino]butyl]-1-(9H-fluoren-9-yl)-11-(1H-indol-3-ylmethyl)-17-isopropyl-3,6,9,12,15,18-hexaoxo-2-oxa-4,7,10,13,16,19-hexaazatricosan-23-oic acid | C87H113N11O15 | 详情 | 详情 | |
| (XVII) | 18863 | 9H-fluoren-9-ylmethyl (5S,8S,11R,14S,17S)-19-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-5-benzyl-8-[4-(tert-butoxy)benzyl]-14-[4-[(tert-butoxycarbonyl)amino]butyl]-11-(1H-indol-3-ylmethyl)-17-isopropyl-6,9,12,15,18,23-hexaoxo-1,4,7,10,13,16,19-heptaazacyclotricosane-4-carboxylate | C87H111N11O14 | 详情 | 详情 |