|
【结 构 式】 
|
【分子编号】61398 【品名】(2S)-1-{(2S,5S,8S,11S,12R)-11-amino-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-12,14,14-trimethyl-5-[(1S)-1-methylpropyl]-4,7,10-trioxo-8-propyl-13-oxa-3,6,9-triazapentadec-1-anoyl}-2-pyrrolidinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C44H76N8O10S 【 分 子 量 】909.20136 【元素组成】C 58.13% H 8.43% N 12.32% O 17.6% S 3.53% |
合成路线1
该中间体在本合成路线中的序号：(X)The title compound is prepared by solid-phase peptide synthesis using an automatic peptide synthesizer. To the L-proline attached to the resin support (I) is coupled Fmoc-L-Arg(Pmc)-OH (II) under activation with HBTU/HOBt to produce the protected dipeptide resin (III). The N-Fmoc group of (III) is then removed by means of piperidine in DMF, yielding the deprotected amine (IV). Subsequent coupling with N-Fmoc-L-isoleucine (V), followed by deprotection with piperidine in DMF, leads to the tripeptide resin (VI). Further coupling/deprotection cycles with N-Fmoc-L-norvaline (VII) and N-Fmoc-O-t-butyl-L-threonine (IX) produce resins (VIII) and (X) respectively.
| 【1】 Haviv, F.; Kalvin, D.M.; Henkin, J.; Bradley, M.F.; Schneider, A.J. (Abbott Laboratories Inc.); Peptide antiangiogenic drugs. JP 2002516342; WO 9961476 . |
| 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) | 16731 | L-proline | 147-85-3 | C5H9NO2 | 详情 | 详情 |
| (II) | 49886 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid | C35H44N4O7S | 详情 | 详情 | |
| (III) | 61391 | (2S)-1-{(2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid | C40H51N5O8S | 详情 | 详情 | |
| (IV) | 61392 | (2S)-1-{(2S)-2-amino-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid | C25H41N5O6S | 详情 | 详情 | |
| (V) | 61393 | (2S,3S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (VI) | 61394 | (2S)-1-{(2S)-2-{[(2S,3S)-2-amino-3-methylpentanoyl]amino}-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid | C31H52N6O7S | 详情 | 详情 | |
| (VII) | 61395 | (2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}pentanoic acid | C20H21NO4 | 详情 | 详情 | |
| (VIII) | 61396 | (2S)-1-{(2S)-2-[((2S,3S)-2-{[(2S)-2-aminopentanoyl]amino}-3-methylpentanoyl)amino]-5-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]pentanoyl}-2-pyrrolidinecarboxylic acid | C36H61N7O8S | 详情 | 详情 | |
| (IX) | 61397 | tert-butyl (2S,3R)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-hydroxybutanoate | C23H27NO5 | 详情 | 详情 | |
| (X) | 61398 | (2S)-1-{(2S,5S,8S,11S,12R)-11-amino-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-12,14,14-trimethyl-5-[(1S)-1-methylpropyl]-4,7,10-trioxo-8-propyl-13-oxa-3,6,9-triazapentadec-1-anoyl}-2-pyrrolidinecarboxylic acid | C44H76N8O10S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)To the peptide resin (X) are sequentially coupled N-Fmoc-D-isoleucine (XI), N-Fmoc-L-valine (XIII), and N-Fmoc-glycine (XV) to produce - after the corresponding deprotection steps with piperidine in DMF- the peptide resins (XII), (XIV) and (XVI) respectively.
| 【1】 Haviv, F.; Kalvin, D.M.; Henkin, J.; Bradley, M.F.; Schneider, A.J. (Abbott Laboratories Inc.); Peptide antiangiogenic drugs. JP 2002516342; WO 9961476 . |
| 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) | 61398 | (2S)-1-{(2S,5S,8S,11S,12R)-11-amino-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-12,14,14-trimethyl-5-[(1S)-1-methylpropyl]-4,7,10-trioxo-8-propyl-13-oxa-3,6,9-triazapentadec-1-anoyl}-2-pyrrolidinecarboxylic acid | C44H76N8O10S | 详情 | 详情 | |
| (XI) | 49375 | (2R,3S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (XII) | 61399 | (2S)-1-{(2S,5S,8S,11S,14R,15S)-14-amino-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-15-methyl-5-[(1S)-1-methylpropyl]-4,7,10,13-tetraoxo-8-propyl-3,6,9,12-tetraazaheptadec-1-anoyl}-2-pyrrolidinecarboxylic acid | C50H87N9O11S | 详情 | 详情 | |
| (XIII) | 19932 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid | C20H21NO4 | 详情 | 详情 | |
| (XIV) | 61400 | (2S)-1-{(2S,5S,8S,11S,14R,17S)-17-amino-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-18-methyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16-pentaoxo-8-propyl-3,6,9,12,15-pentaazanonadec-1-anoyl}-2-pyrrolidinecarboxylic acid | C55H96N10O12S | 详情 | 详情 | |
| (XV) | 42131 | 2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid | 29022-11-5 | C17H15NO4 | 详情 | 详情 |
| (XVI) | 61401 | (2S)-1-{(2S,5S,8S,11S,14R,17S)-20-amino-11-[(1R)-1-(tert-butoxy)ethyl]-2-{3-[(imino{[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino}methyl)amino]propyl}-17-isopropyl-5,14-bis[(1S)-1-methylpropyl]-4,7,10,13,16,19-hexaoxo-8-propyl-3,6,9,12,15,18-hexaazaicos-1-anoyl}-2-pyrrolidinecarboxylic acid | C57H99N11O13S | 详情 | 详情 |