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【结 构 式】 
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【分子编号】34768 【品名】tert-butyl (5S)-6-amino-5-({[(2S)-1-((2S,5R,8S,11S)-11-amino-16-imino-2,8-bis{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5-methyl-4,7,10-trioxo-16-{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}-3,6,9,15-tetraazahexadec-1-anoyl)pyrrolidinyl]carbonyl}amino)-6-oxohexylcarbamate 【CA登记号】 |
【 分 子 式 】C76H119N17O17S3 【 分 子 量 】1639.08324 【元素组成】C 55.69% H 7.32% N 14.53% O 16.59% S 5.87% |
合成路线1
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 poliethylene glycol amino resin. Coupling with N(alpha)-Fmoc-N(G)-Boc-lysine (I) using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and N-methylmorpholine (NMM) afforded the protected lysine-linked resin (II), and subsequent Fmoc deprotection provided resin (III). This was submitted to further coupling and deprotection cycles with the N(alpha)-Fmoc-protected amino acids proline (IV), N(G)-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)arginine (VI), D-alanine (VIII), N(G)-Pbf-arginine (VI), and again N(G)-Pbf-arginine (VI) yielding peptide resins (V), (VII), (IX), (X) and (XI).
| 【1】 Aldrich, J.V.; Murray, T.F.; Wan, Q.; A novel acetylated analogue of dynorphin A-(1-11) amide as a kappa-opioid receptor antagonist. J Med Chem 1999, 42, 16, 3011. |
| 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) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (II) | 28723 | 9H-fluoren-9-ylmethyl (1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentylcarbamate | C26H33N3O5 | 详情 | 详情 | |
| (III) | 34761 | tert-butyl (5S)-5,6-diamino-6-oxohexylcarbamate | C11H23N3O3 | 详情 | 详情 | |
| (IV) | 34762 | (2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid | 71989-31-6 | C20H19NO4 | 详情 | 详情 |
| (V) | 34763 | tert-butyl (5S)-6-amino-6-oxo-5-[[(2S)pyrrolidinylcarbonyl]amino]hexylcarbamate | C16H30N4O4 | 详情 | 详情 | |
| (VI) | 34764 | (2S)-5-[[[[(9H-fluoren-9-ylmethoxy)carbonyl]amino](imino)methyl]amino]-2-[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]pentanoic acid | C34H40N4O7S | 详情 | 详情 | |
| (VII) | 34765 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-amino-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C35H58N8O8S | 详情 | 详情 | |
| (VIII) | 19926 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C18H17NO4 | 详情 | 详情 | |
| (IX) | 34766 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-[[(2R)-2-aminopropanoyl]amino]-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C38H63N9O9S | 详情 | 详情 | |
| (X) | 34767 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-[[(2R)-2-([(2S)-2-amino-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]amino)propanoyl]amino]-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C57H91N13O13S2 | 详情 | 详情 | |
| (XI) | 34768 | tert-butyl (5S)-6-amino-5-({[(2S)-1-((2S,5R,8S,11S)-11-amino-16-imino-2,8-bis{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5-methyl-4,7,10-trioxo-16-{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}-3,6,9,15-tetraazahexadec-1-anoyl)pyrrolidinyl]carbonyl}amino)-6-oxohexylcarbamate | C76H119N17O17S3 | 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 coupling and deprotection cycles were continued with leucine (XII), N(in)-Boc-tryptophan (XIV), and again N(in)-Boc-tryptophan (XIV) affording peptide resins (XIII), (XV) and (XVI).
| 【1】 Aldrich, J.V.; Murray, T.F.; Wan, Q.; A novel acetylated analogue of dynorphin A-(1-11) amide as a kappa-opioid receptor antagonist. J Med Chem 1999, 42, 16, 3011. |
| 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) | 34768 | tert-butyl (5S)-6-amino-5-({[(2S)-1-((2S,5R,8S,11S)-11-amino-16-imino-2,8-bis{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5-methyl-4,7,10-trioxo-16-{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}-3,6,9,15-tetraazahexadec-1-anoyl)pyrrolidinyl]carbonyl}amino)-6-oxohexylcarbamate | C76H119N17O17S3 | 详情 | 详情 | |
| (XII) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (XII) | 34769 | tert-butyl (5S)-6-amino-5-({[(2S)-1-((2S,5R,8S,11S,14S)-14-amino-2,8,11-tris{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5,16-dimethyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaheptadec-1-anoyl)pyrrolidinyl]carbonyl}amino)-6-oxohexylcarbamate | C82H130N18O18S3 | 详情 | 详情 | |
| (XIV) | 34770 | (2S)-2-[(tert-butoxycarbonyl)[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(1H-indol-3-yl)propionic acid | C31H30N2O6 | 详情 | 详情 | |
| (XV) | 34771 | tert-butyl 3-((2S,5S,8S,11S,14R,17S)-2-amino-17-({(2S)-2-[({(1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentyl}amino)carbonyl]pyrrolidinyl}carbonyl)-22-imino-8,11-bis{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5-isobutyl-14-methyl-3,6,9,12,15-pentaoxo-22-{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}-4,7,10,13,16,21-hexaazadocos-1-yl)-1H-indole-1-carboxylate | C98H148N20O21S3 | 详情 | 详情 | |
| (XVI) | 34772 | C114H166N22O24S3 | 详情 | 详情 |