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【结 构 式】 
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【分子编号】31377 【品名】S-[(2R,5S,8S)-8-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate 【CA登记号】 |
【 分 子 式 】C56H65ClN8O9S 【 分 子 量 】1061.69932 【元素组成】C 63.35% H 6.17% Cl 3.34% N 10.55% O 13.56% S 3.02% |
合成路线1
该中间体在本合成路线中的序号：(XII)Compound (X) was subsequently submitted to further coupling and deprotection cycles with the protected amino acids N-Boc-D-tryptophan (XI) and N-Boc-L-(3-pyridyl)alanine (XIII) to afford the peptide-resins (XII) and (XIV), respectively.
| 【1】 Taylor, J.E.; Hocart, S.J.; Murphy, W.A.; Coy, D.H.; Jian, R.; Highly potent cyclic disulfide antagonists of somatostatin. J Med Chem 1999, 42, 11, 1863. |
| 【2】 Murphy, W.; Coy, D.H.; Morgan, B. (Biomeasure Inc.; Tulane Educational Fund); Somatostatin antagonists. WO 9824807 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 31375 | S-[(2R,5S,8S)-8-amino-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate | C45H55ClN6O8S | 详情 | 详情 | |
| (XI) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (XII) | 31377 | S-[(2R,5S,8S)-8-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate | C56H65ClN8O9S | 详情 | 详情 | |
| (XIII) | 31378 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3-pyridinyl)propionic acid | C13H18N2O4 | 详情 | 详情 | |
| (XIV) | 31376 | S-[(2R,5S,8S)-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-8-[[(2R)-2-[[(2S)-2-amino-3-(3-pyridinyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec- | C64H73ClN10O10S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)The compound was prepared by solid-phase peptide synthesis on a 4-methylbenzhydrylamine-functionalized resin using an automatic peptide synthesizer. Binding of N-Boc-3-(2-naphthyl)-L-alanine (I) to the resin was effected by double coupling, first with the 1,3-diisopropylcarbodiimide active ester, and then a second coupling with the TBTU ester to produce the amino acid-linked resin (II). Deblocking of the Boc group of (II) by treatment with trifluoroacetic acid provided resin (III). The following amino acids were then coupled and deprotected successively to (III) by the same procedure: N-Boc-S-(4-methylbenzyloxycarbonyl)-L-cysteine (IV), N-Boc-L-tert-leucine (VI), N(alpha)-Boc-N(epsilon)-(2-chlorobenzyloxycarbonyl)-L-lysine (VIII) and N-Boc-D-tryptophan (X) yielding the peptide resins (V), (VII), (IX) and (XI), respectively.
| 【1】 Rossowski, W.J.; Cheng, B.-L.; Jiang, N.-Y.; Coy, D.-H.; Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue. Br J Pharmacol 1998, 125, 1081. |
| 【2】 Taylor, J.E.; Hocart, S.J.; Murphy, W.A.; Coy, D.H.; Jian, R.; Highly potent cyclic disulfide antagonists of somatostatin. J Med Chem 1999, 42, 11, 1863. |
| 【3】 Murphy, W.; Coy, D.H.; Morgan, B. (Biomeasure Inc.; Tulane Educational Fund); Somatostatin antagonists. WO 9824807 . |
| 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) | 15061 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(2-naphthyl)propionic acid; N-T-BOC-L-3-(2-NAPHTHYL)ALANINE | 58438-04-3 | C18H21NO4 | 详情 | 详情 |
| (II) | 31369 | tert-butyl (1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethylcarbamate | C18H22N2O3 | 详情 | 详情 | |
| (III) | 31370 | (2S)-2-amino-3-(2-naphthyl)propanamide | C13H14N2O | 详情 | 详情 | |
| (IV) | 31371 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-([[(4-methylbenzyl)oxy]carbonyl]sulfanyl)propionic acid | C17H23NO6S | 详情 | 详情 | |
| (V) | 31372 | S-((2R)-2-amino-3-[[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]-3-oxopropyl) O-(4-methylbenzyl) carbonothioate | C25H27N3O4S | 详情 | 详情 | |
| (VI) | 22251 | (2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutyric acid;2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoic acid;N-(tert-butoxycarbonyl)-3-methyl-L-valine | 62965-35-9 | C11H21NO4 | 详情 | 详情 |
| (VII) | 31373 | S-((2R)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-3-[[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]-3-oxopropyl) O-(4-methylbenzyl) carbonothioate | C31H38N4O5S | 详情 | 详情 | |
| (VIII) | 31374 | (2S)-2-[(tert-butoxycarbonyl)amino]-6-([[(2-chlorobenzyl)oxy]carbonyl]amino)hexanoic acid | C19H27ClN2O6 | 详情 | 详情 | |
| (IX) | 31375 | S-[(2R,5S,8S)-8-amino-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate | C45H55ClN6O8S | 详情 | 详情 | |
| (X) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (XI) | 31377 | S-[(2R,5S,8S)-8-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate | C56H65ClN8O9S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XI)The coupling and deprotection cycles was continued with N-Boc-L-(3-pyridyl)alanine (XII), N-Boc-S-(4-methylbenzyloxy-carbonyl)-D-cysteine (IV), and N-Boc-L-4-fluorophenylalanine (XV), yielding the peptide resins (XIII), (XIV) and (XVI), respectively.
| 【1】 Taylor, J.E.; Hocart, S.J.; Murphy, W.A.; Coy, D.H.; Jian, R.; Highly potent cyclic disulfide antagonists of somatostatin. J Med Chem 1999, 42, 11, 1863. |
| 【2】 Rossowski, W.J.; Cheng, B.-L.; Jiang, N.-Y.; Coy, D.-H.; Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue. Br J Pharmacol 1998, 125, 1081. |
| 【3】 Murphy, W.; Coy, D.H.; Morgan, B. (Biomeasure Inc.; Tulane Educational Fund); Somatostatin antagonists. WO 9824807 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 31371 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-([[(4-methylbenzyl)oxy]carbonyl]sulfanyl)propionic acid | C17H23NO6S | 详情 | 详情 | |
| (XI) | 31377 | S-[(2R,5S,8S)-8-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate | C56H65ClN8O9S | 详情 | 详情 | |
| (XII) | 34944 | (2S)-2-[(tert-butoxycarbonyl)(3-pyridinyl)amino]propionic acid | C13H18N2O4 | 详情 | 详情 | |
| (XIII) | 31376 | S-[(2R,5S,8S)-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-8-[[(2R)-2-[[(2S)-2-amino-3-(3-pyridinyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec- | C64H73ClN10O10S | 详情 | 详情 | |
| (XIV) | 31379 | S-[(2R,5S,8S,11R,14S,17S)-17-amino-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-8-[4-([[(2-chlorobenzyl)oxy]carbonyl]amino)butyl]-11-(1H-indol-3-ylmethyl)-22-(4-methylphenyl)-4,7,10,13,16,20-hexaoxo-14-(3-pyridiny | C76H86ClN11O13S2 | 详情 | 详情 | |
| (XV) | 25929 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propionic acid | C14H18FNO4 | 详情 | 详情 | |
| (XVI) | 34945 | C90H102ClFN12O16S2 | 详情 | 详情 |