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【结 构 式】 
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【分子编号】29884 【品名】(3R,4E)-3-hydroxy-7-(tritylsulfanyl)-4-heptenoic acid 【CA登记号】 |
【 分 子 式 】C26H26O3S 【 分 子 量 】418.55664 【元素组成】C 74.61% H 6.26% O 11.47% S 7.66% |
合成路线1
该中间体在本合成路线中的序号：(VIII)(ii) The asymmetric construction of the hydroxymercaptoheptenoic acid: For construction of the hydroxymercaptoheptenoic acid (VIII), cesium triphenylmethylthiolate anion was added to methyl 2,4-pentadienoate (V), which resulted in a beta,gamma-unsaturated methyl ester that was converted to an alpha,beta-unsaturated ester after exposure to Cs2CO3. DIBAL reduction to the primary alcohol followed by Swern oxidation yielded the alpha,beta-unsaturated aldehyde (VI). In the presence of the ligand derived from (R)-(-)-binaphthyl amino alcohol, Ti(IV)-catalyzed addition of O-benzyl, O-TMS ketene acetal to the alpha,beta-unsaturated aldehyde (VI) resulted in the aldol product (VII). Hydrolysis of the benzyl ester with LiOH in aqueous methanol formed the beta-hydroxymercaptoheptenoic acid (VIII).
| 【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 |
|---|---|---|---|---|---|---|
| 29882 | [[1-(benzyloxy)vinyl]oxy](trimethyl)silane; benzyl 1-[(trimethylsilyl)oxy]vinyl ether | C12H18O2Si | 详情 | 详情 | ||
| (V) | 29880 | methyl (2E)-2,4-pentadienoate | C6H8O2 | 详情 | 详情 | |
| (VI) | 29881 | (E)-5-(tritylsulfanyl)-2-pentenoic acid | C24H22O2S | 详情 | 详情 | |
| (VII) | 29883 | benzyl (3R,4E)-3-hydroxy-7-(tritylsulfanyl)-4-heptenoate | C33H32O3S | 详情 | 详情 | |
| (VIII) | 29884 | (3R,4E)-3-hydroxy-7-(tritylsulfanyl)-4-heptenoic acid | C26H26O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)(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 |