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【结 构 式】 
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【分子编号】49360 【品名】tert-butyl (6R,7S,8S,12Z,15S,16E)-15-hydroxy-4,4,6,8,12,16-hexamethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-12,16-heptadecadienoate 【CA登记号】 |
【 分 子 式 】C37H51Cl6NO11S 【 分 子 量 】930.59428 【元素组成】C 47.76% H 5.52% Cl 22.86% N 1.51% O 18.91% S 3.45% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The treatment of diketoester (XII) with trimethylsilyl diazomethane and DIEA gives enol ether (XIII), which is condensed with 2(S)-methyl-4-pentenal (XIV) by means of LDA to yield the aldol condensation product (XV) as the major isomer. The protection of the OH group of (XV) with Troc-Cl and pyridine affords the trichloroethyl carbonate (XVI), whose enol ether group is hydrolyzed with TsOH in acetone to provide the diketoester (XVII). The condensation of (XVII) with iodovinyl intermediate (XI) by means of BBN, (dppf)2PdCl2, AsPh3 and Cs2CO3 in THF/DMF/water gives adduct (XVIII), which is desilylated by means of HCl in methanol to yield the secondary alcohol (XIX). The asymmetric hydrogenation of (XIX) with H2 over a chiral Ru catalyst in acidic methanol affords the secondary diol (XX), which is silylated with Tes-OTf and lutidine to provide the bis-silyl ether (XXI). The selective desilylation of (XXI) with simultaneous hydrolysis of its tert-butyl ester by means of HCl in methanol gives the hydroxyacid (XXII) suitable for cyclization.
| 【1】 Zhang, X.-G.; Chappell, M.D.; Lee, C.B.; Kuduk, S.D.; Danishefsky, S.J.; Chou, T.-C.; Wang, Z.-G.; Stachel, S.J.; Total synthesis and antitumor activity of 12,13-dexoxyepothilone F: An unexpected solvolysis problem at C15, mediated by remote substitution at C21. J Org Chem 2000, 65, 20, 6525. |
| 【2】 Harris, C.R.; et al.; New chemical synthesis of the promising cancer chemotherapeutic agent 12,13-desoxyepothilone B: Discovery of a surprising long-range effect on the diastereoselectivity of an aldol condensation. J Am Chem Soc 1999, 121, 30, 7050. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 49358 | [4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-heptadienyl)-1,3-thiazol-2-yl]methyl 2,2,2-trichloroethyl carbonate | C21H31Cl3INO4SSi | 详情 | 详情 | |
| (XII) | 26239 | tert-butyl 4,4-dimethyl-3,5-dioxoheptanoate | C13H22O4 | 详情 | 详情 | |
| (XIII) | 26240 | tert-butyl (Z)-3-methoxy-4,4-dimethyl-5-oxo-2-heptenoate | C14H24O4 | 详情 | 详情 | |
| (XIV) | 26241 | (2S)-2-methyl-4-pentenal | C6H10O | 详情 | 详情 | |
| (XV) | 26242 | tert-butyl (2Z,6R,7S,8S)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxo-2,10-undecadienoate | C20H34O5 | 详情 | 详情 | |
| (XVI) | 26243 | tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-2,10-undecadienoate | C23H35Cl3O7 | 详情 | 详情 | |
| (XVII) | 26244 | tert-butyl (6R,7S,8S)-4,4,6,8-tetramethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-10-undecenoate | C22H33Cl3O7 | 详情 | 详情 | |
| (XVIII) | 49359 | tert-butyl (6R,7S,8S,12Z,15S,16E)-15-[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-12,16-heptadecadienoate | C43H65Cl6NO11SSi | 详情 | 详情 | |
| (XIX) | 49360 | tert-butyl (6R,7S,8S,12Z,15S,16E)-15-hydroxy-4,4,6,8,12,16-hexamethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-12,16-heptadecadienoate | C37H51Cl6NO11S | 详情 | 详情 | |
| (XX) | 49361 | tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-3,15-dihydroxy-4,4,6,8,12,16-hexamethyl-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-12,16-heptadecadienoate | C37H53Cl6NO11S | 详情 | 详情 | |
| (XXI) | 49362 | tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-4,4,6,8,12,16-hexamethyl-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-3,15-bis[(triethylsilyl)oxy]-12,16-heptadecadienoate | C49H81Cl6NO11SSi2 | 详情 | 详情 | |
| (XXII) | 49363 | (3S,6R,7S,8S,12Z,15S,16E)-15-hydroxy-4,4,6,8,12,16-hexamethyl-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-17-[2-([[(2,2,2-trichloroethoxy)carbonyl]oxy]methyl)-1,3-thiazol-4-yl]-3-[(triethylsilyl)oxy]-12,16-heptadecadienoic acid | C39H59Cl6NO11SSi | 详情 | 详情 |