|
【结 构 式】 
|
【分子编号】54612 【品名】benzyl (1S)-1-{[{(1S,2R)-2-methoxy-4-[(2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl)pyrrolidinyl]-1-[(1S)-1-methylpropyl]-4-oxobutyl}(methyl)amino]carbonyl}-2-methylpropylcarbamate 【CA登记号】 |
【 分 子 式 】C43H61N5O7S 【 分 子 量 】792.05284 【元素组成】C 65.21% H 7.76% N 8.84% O 14.14% S 4.05% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)The condensation of intermediate (XXI) with intermediate (XV) by means of BOP and DIEA gives the dipeptide (XXIV) partially racemized, which is easily purified by chromatography. The deprotection of (XXIV) by means of TFA yields dipeptide (XXV), which is condensed with intermediate (VIII) by means of BOP and DIEA to afford tripeptide (XXVI). The deprotection of (XXVI) by means of TFA yields tripeptide (XXVII), which is condensed with N-(benzyloxycarbonyl)-L-valine (XXVIII) by means of BrOP and DIEA to afford tetrapeptide (XXIX). The deprotection of (XXIX) by means of HBr provides tetrapeptide (XXX), which is finally condensed with N,N-dimethyl-L-valine (XXXI) by means of COMMOD to afford the target dolastatine.
| 【1】 Roux, F.; et al.; Synthesis of dolastatin-10 and [R-Doe]-dolastatin-10. Tetrahedron 1994, 50, 18, 5345. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 54599 | (3R,4S)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid | C15H29NO5 | 详情 | 详情 | |
| (XV) | 23520 | (2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-3-methoxy-2-methylpropionic acid | C14H25NO5 | 详情 | 详情 | |
| (XXI) | 54607 | (1S)-2-phenyl-1-(1,3-thiazol-2-yl)-1-ethanamine; (1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethylamine | C11H12N2S | 详情 | 详情 | |
| (XXIV) | 54608 | tert-butyl (2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl)-1-pyrrolidinecarboxylate | C25H35N3O4S | 详情 | 详情 | |
| (XXV) | 54609 | (2R,3R)-3-methoxy-2-methyl-N-[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]-3-[(2S)pyrrolidinyl]propanamide | C20H27N3O2S | 详情 | 详情 | |
| (XXVI) | 54610 | tert-butyl (1S,2R)-2-methoxy-4-[(2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl)pyrrolidinyl]-1-[(1S)-1-methylpropyl]-4-oxobutyl(methyl)carbamate | C35H54N4O6S | 详情 | 详情 | |
| (XXVII) | 54611 | (2R,3R)-3-methoxy-3-{(2S)-1-[(3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl]pyrrolidinyl}-2-methyl-N-[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]propanamide | C30H46N4O4S | 详情 | 详情 | |
| (XXVIII) | 49332 | (2R)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid | C13H17NO4 | 详情 | 详情 | |
| (XXIX) | 54612 | benzyl (1S)-1-{[{(1S,2R)-2-methoxy-4-[(2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl)pyrrolidinyl]-1-[(1S)-1-methylpropyl]-4-oxobutyl}(methyl)amino]carbonyl}-2-methylpropylcarbamate | C43H61N5O7S | 详情 | 详情 | |
| (XXX) | 54613 | (2S)-2-amino-N-{(1S,2R)-2-methoxy-4-[(2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl)pyrrolidinyl]-1-[(1S)-1-methylpropyl]-4-oxobutyl}-N,3-dimethylbutanamide | C35H55N5O5S | 详情 | 详情 | |
| (XXXI) | 23518 | (2S)-2-(dimethylamino)-3-methylbutyric acid | C7H15NO2 | 详情 | 详情 |