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【结 构 式】 
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【分子编号】44500 【品名】isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate 【CA登记号】 |
【 分 子 式 】C44H71NO7SSi 【 分 子 量 】786.20178 【元素组成】C 67.22% H 9.1% N 1.78% O 14.25% S 4.08% Si 3.57% |
合成路线1
该中间体在本合成路线中的序号：(XXXIV)Assembly of the target compound: The condensation of intermediates (XVI) and (XXVII) by means of 9-BBN, a Pd catalyst and Cs2CO3 in THF/DMF gives the adduct (XXVIII), which is selectively deprotected with HF/pyridine in THF, yielding the primary alcohol (XXIX). The oxidation of (XXIX) with DMP in dichloromethane affords the aldehyde (XXX), which is condensed with the silyl enol ether (XXXI) by means of TiCl4 in dichloromethane to provide the isopropyl carboxylate (XXXII). The desilylation of (XXXII) with TBAF in THF gives the dihydroxyester (XXXIII), which is selectively monosilylated with Tbdms-Cl and imidazole, yielding the hydroxyester (XXXIV). The oxidation of (XXXIV) with DMP in dichloromethane affords the ketoester (XXXV), which was submitted to a basic hydrolysis of its acetoxy and isopropyl ester groups with NaOH in refluxing methanol to furnish the hydroxyacid (XXXVI).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 44487 | (5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether | C32H60O3Si2 | 详情 | 详情 | |
| (XXVII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 | |
| (XXVIII) | 44494 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11,13-bis[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate | C45H77NO5SSi2 | 详情 | 详情 | |
| (XXIX) | 44495 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-13-hydroxy-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate | C39H63NO5SSi | 详情 | 详情 | |
| (XXX) | 44496 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13-oxo-3-tridecenyl acetate | C39H61NO5SSi | 详情 | 详情 | |
| (XXXI) | 44497 | 1-isopropoxyvinyl trimethylsilyl ether; [(1-isopropoxyvinyl)oxy](trimethyl)silane | C8H18O2Si | 详情 | 详情 | |
| (XXXII) | 44498 | isopropyl (3S,5R,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C44H71NO7SSi | 详情 | 详情 | |
| (XXXIII) | 44499 | isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C38H57NO7S | 详情 | 详情 | |
| (XXXIV) | 44500 | isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C44H71NO7SSi | 详情 | 详情 | |
| (XXXV) | 44501 | isopropyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | C44H69NO7SSi | 详情 | 详情 | |
| (XXXVI) | 44502 | (3S,6R,7S,8S,12Z,15S,16E)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H61NO6SSi | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIV)Assembly of the target compound: The condensation of intermediates (XVI) and (XXVII) by means of 9-BBN, a Pd catalyst and Cs2CO3 in THF/DMF gives the adduct (XXVIII), which is selectively deprotected with HF/pyridine in THF, yielding the primary alcohol (XXIX). The oxidation of (XXIX) with DMP in dichloromethane affords the aldehyde (XXX), which is condensed with the silyl enol ether (XXXI) by means of TiCl4 in dichloromethane to provide the isopropyl carboxylate (XXXII). The desilylation of (XXXII) with TBAF in THF gives the dihydroxyester (XXXIII), which is selectively monosilylated with Tbdms-Cl and imidazole, yielding the hydroxyester (XXXIV). The oxidation of (XXXIV) with DMP in dichloromethane affords the ketoester (XXXV), which was submitted to a basic hydrolysis of its acetoxy and isopropyl ester groups with NaOH in refluxing methanol to furnish the hydroxyacid (XXXVI).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 44487 | (5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether | C32H60O3Si2 | 详情 | 详情 | |
| (XXVII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 | |
| (XXVIII) | 44494 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11,13-bis[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate | C45H77NO5SSi2 | 详情 | 详情 | |
| (XXIX) | 44495 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-13-hydroxy-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate | C39H63NO5SSi | 详情 | 详情 | |
| (XXX) | 44496 | (1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13-oxo-3-tridecenyl acetate | C39H61NO5SSi | 详情 | 详情 | |
| (XXXI) | 44497 | 1-isopropoxyvinyl trimethylsilyl ether; [(1-isopropoxyvinyl)oxy](trimethyl)silane | C8H18O2Si | 详情 | 详情 | |
| (XXXII) | 44498 | isopropyl (3S,5R,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C44H71NO7SSi | 详情 | 详情 | |
| (XXXIII) | 44499 | isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C38H57NO7S | 详情 | 详情 | |
| (XXXIV) | 44500 | isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate | C44H71NO7SSi | 详情 | 详情 | |
| (XXXV) | 44501 | isopropyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | C44H69NO7SSi | 详情 | 详情 | |
| (XXXVI) | 44502 | (3S,6R,7S,8S,12Z,15S,16E)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H61NO6SSi | 详情 | 详情 |