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【结 构 式】 
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【分子编号】29879 【品名】methyl (2S)-2-[((Z)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-(tritylsulfanyl)propanoyl]amino]-2-butenoyl)amino]-3-methylbutanoate 【CA登记号】 |
【 分 子 式 】C37H46N4O5S 【 分 子 量 】658.8622 【元素组成】C 67.45% H 7.04% N 8.5% O 12.14% S 4.87% |
合成路线1
该中间体在本合成路线中的序号：(IV)(i) The formation of a 16-membered depsipeptide: For the first step, L-valine methyl ester (I) was coupled to N-Fmoc-L-threonine using the BOP reagent [(benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate], removing the N-Fmoc group with Et2NH and coupling to N-Fmoc-(S-triphenylmethyl)-D-cysteine to yield the tripeptide (II). The tetrapeptide (III) was prepared by deprotection of the tripeptide (II) and BOP-mediated peptide coupling of the resulting amine with N-Fmoc-D-valine. The secondary hydroxyl group was activated as the tosylate and eliminated by treatment with DABCO to produce the internal alkene. After removal of the Fmoc protecting group by addition of Et2NH to the reaction mixture, the 16-membered depsipeptide (IV) was formed.
| 【1】 Li, K.W.; Simon, J.A.; Xing, W.; Wu, J.; Total synthesis of the antitumor depsipeptide FR901228. J Am Chem Soc 1996, 118, 30, 7237. |
| 【2】 Wang, H.-C. R.; FR901228. Drugs Fut 1999, 24, 11, 1184. |
| 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) | 16613 | methyl (2S)-2-amino-3-methylbutanoate | C6H13NO2 | 详情 | 详情 | |
| (II) | 29877 | methyl (5S,8S,11S)-1-(9H-fluoren-9-yl)-8-[(1R)-1-hydroxyethyl]-11-isopropyl-3,6,9-trioxo-5-[(tritylsulfanyl)methyl]-2-oxa-4,7,10-triazadodecan-12-oate | C47H49N3O7S | 详情 | 详情 | |
| (III) | 29878 | methyl (5R,8S,11S,14S)-1-(9H-fluoren-9-yl)-5,14-diisopropyl-11-((1R)-1-[[(4-methylphenyl)sulfonyl]oxy]ethyl)-3,6,9,12-tetraoxo-8-[(tritylsulfanyl)methyl]-2-oxa-4,7,10,13-tetraazapentadecan-15-oate | C59H64N4O10S2 | 详情 | 详情 | |
| (IV) | 29879 | methyl (2S)-2-[((Z)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-(tritylsulfanyl)propanoyl]amino]-2-butenoyl)amino]-3-methylbutanoate | C37H46N4O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)(iii) An intramolecular oxidative coupling of the thiols to form a 15-membered disulfide-containing ring: To complete the synthesis of FR901228, the beta-hydroxymercaptoheptenoic acid (VIII) was coupled to the 16-membered cyclic depsipeptide (IV) using the BOP reagent, followed by LiOH-mediated hydrolysis, resulting in the free acid product (IX). Cyclization of the hydroxy acid (IX) with TsOH, DEAD and PPh3 and oxidation of the bis(S-triphenylmethyl)lactone (X) with iodine in methanol solution yielded the depsipeptide FR901228.
| 【1】 Wang, H.-C. R.; FR901228. Drugs Fut 1999, 24, 11, 1184. |
| 【2】 Li, K.W.; Simon, J.A.; Xing, W.; Wu, J.; Total synthesis of the antitumor depsipeptide FR901228. J Am Chem Soc 1996, 118, 30, 7237. |
| 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) | 29879 | methyl (2S)-2-[((Z)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-(tritylsulfanyl)propanoyl]amino]-2-butenoyl)amino]-3-methylbutanoate | C37H46N4O5S | 详情 | 详情 | |
| (VIII) | 29884 | (3R,4E)-3-hydroxy-7-(tritylsulfanyl)-4-heptenoic acid | C26H26O3S | 详情 | 详情 | |
| (IX) | 29885 | (E,7R,11R,14S,20S)-17-[(Z)ethylidene]-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-[(tritylsulfanyl)methyl]-2-thia-10,13,16,19-tetraaza-5-henicosen-21-oic acid | C62H68N4O7S2 | 详情 | 详情 | |
| (X) | 29886 | (3S,9S,12R,16S)-6-[(Z)ethylidene]-3,12-diisopropyl-16-[(E)-4-(tritylsulfanyl)-1-butenyl]-9-[(tritylsulfanyl)methyl]-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentone | C62H66N4O6S2 | 详情 | 详情 |