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【结 构 式】 
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【分子编号】28723 【品名】9H-fluoren-9-ylmethyl (1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentylcarbamate 【CA登记号】 |
【 分 子 式 】C26H33N3O5 【 分 子 量 】467.56524 【元素组成】C 66.79% H 7.11% N 8.99% O 17.11% |
合成路线1
该中间体在本合成路线中的序号：(II)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：(III)The successive condensations of fluorenylmethoxycarbonyl-Rink amide resin (I) with Nalpha-FMOC-Nepsilon-Boc-L-lysine (II), FMOC-D-phenylalanine (IV), FMOC-D-2-naphthylalanine (VI), FMOC-Npi-trityl-L-histidine (VIII), and finally 2-(tert-butoxycarbonylamino)isobutyric acid (X), using the solid phase peptide technique synthesis yielded resins (III), (V), (VII), (IX) and finally (XI). This last resin was then treated with trifluoroacetic acid in order to eliminate the Boc protecting groups and the solid phase resin and isolate the target compound.
| 【1】 Muller, L.; et al.; C-14-labelling of ipamorelin, a growth hormone secretagogue. J Label Compd Radiopharm 1998, 41, 12, 1093. |
| 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) | 28722 | 9H-fluoren-9-ylmethyl carbamate | 84418-43-9 | C15H13NO2 | 详情 | 详情 |
| (III) | 28723 | 9H-fluoren-9-ylmethyl (1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentylcarbamate | C26H33N3O5 | 详情 | 详情 | |
| (IV) | 28730 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid | C24H21NO4 | 详情 | 详情 | |
| (V) | 28724 | 9H-fluoren-9-ylmethyl (1R)-2-([(1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentyl]amino)-1-benzyl-2-oxoethylcarbamate | C35H42N4O6 | 详情 | 详情 | |
| (VI) | 28725 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-naphthyl)propionic acid | C28H23NO4 | 详情 | 详情 | |
| (VII) | 28726 | 9H-fluoren-9-ylmethyl (1R,4R,7S)-7-(aminocarbonyl)-4-benzyl-15,15-dimethyl-1-(2-naphthylmethyl)-2,5,13-trioxo-14-oxa-3,6,12-triazahexadec-1-ylcarbamate | C48H53N5O7 | 详情 | 详情 | |
| (VIII) | 28727 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(1-trityl-1H-imidazol-5-yl)propionic acid | C40H33N3O4 | 详情 | 详情 | |
| (IX) | 28728 | 9H-fluoren-9-ylmethyl (1S,4R,7R,10S)-10-(aminocarbonyl)-7-benzyl-18,18-dimethyl-4-(2-naphthylmethyl)-2,5,8,16-tetraoxo-1-[(1-trityl-1H-imidazol-5-yl)methyl]-17-oxa-3,6,9,15-tetraazanonadec-1-ylcarbamate | C73H74N8O8 | 详情 | 详情 | |
| (X) | 18471 | N-(tert-butoxycarbonyl)-2-methylalanine | 30992-29-1 | C9H17NO4 | 详情 | 详情 |
| (XI) | 28729 | tert-butyl (4S,7R,10R,13S)-13-(aminocarbonyl)-10-benzyl-1,1,21,21-tetramethyl-7-(2-naphthylmethyl)-2,5,8,11,19-pentaoxo-4-[(1-trityl-1H-imidazol-5-yl)methyl]-20-oxa-3,6,9,12,18-pentaazadocos-1-ylcarbamate | C67H79N9O9 | 详情 | 详情 |