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【结 构 式】 
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【分子编号】54282 【品名】tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetyloxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-[(4-methoxybenzyl)oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate 【CA登记号】n/a |
【 分 子 式 】C46H73NO8SSi 【 分 子 量 】828.23906 【元素组成】C 66.71% H 8.88% N 1.69% O 15.45% S 3.87% Si 3.39% |
合成路线1
该中间体在本合成路线中的序号：(XXX)The Suzuki coupling of the unsaturated ketoester (XXIX) with the omega iodoalkyl thiazole intermediate (XII) by means of PdCl2(dppf)2, AsPh3, Cs2CO3 and 9-BBN gives the heptadienoic ester (XXX), which is treated with MeONa, Tms-OTf and NaOH to yield the hydroxyacid (XXXI). The macrocyclization of (XXXI) under Yamaguchi conditions affords the macrolactone (XXXII), which is treated with DDQ (cleavage of the Pmb group) to provide the still silylated compound (XXXIII). The treatment of (XXXIII) with HF and pyridine (cleavage of the Tbdms group) gives the free macrolactone (XXXIV), which is finally epoxidated by means of DMDO to furnish the target epothilone A.
| 【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 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 | |
| (XXIX) | 54281 | tert-butyl (3S,6R,7S,8S)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-[(4-methoxybenzyl)oxy]-4,4,6,8-tetramethyl-5-oxo-10-undecenoate | n/a | C33H56O6Si | 详情 | 详情 |
| (XXX) | 54282 | tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetyloxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-[(4-methoxybenzyl)oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | n/a | C46H73NO8SSi | 详情 | 详情 |
| (XXXI) | 54283 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-7-[(4-methoxybenzyl)oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | n/a | C40H63NO7SSi | 详情 | 详情 |
| (XXXII) | 54284 | (4S,7R,8S,9S,16S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-[(4-methoxybenzyl)oxy]-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | n/a | C40H61NO6SSi | 详情 | 详情 |
| (XXXIII) | 43176 | (4S,7R,8S,9S,16S)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C32H53NO5SSi | 详情 | 详情 | |
| (XXXIV) | 44447 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C26H39NO5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXX)The Suzuki coupling of the unsaturated ketoester (XXIX) with the omega iodoalkyl thiazole intermediate (XII) by means of PdCl2(dppf)2, AsPh3, Cs2CO3 and 9-BBN gives the heptadienoic ester (XXX), which is treated with MeONa, Tms-OTf and NaOH to yield the hydroxyacid (XXXI). The macrocyclization of (XXXI) under Yamaguchi conditions affords the macrolactone (XXXII), which is treated with DDQ (cleavage of the Pmb group) to provide the still silylated compound (XXXIII). Finally, the treatment of (XXXIII) with HF and pyridine (cleavage of the Tbdms group) gives the the target epothilone C.
| 【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 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 | |
| (XXIX) | 54281 | tert-butyl (3S,6R,7S,8S)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-[(4-methoxybenzyl)oxy]-4,4,6,8-tetramethyl-5-oxo-10-undecenoate | n/a | C33H56O6Si | 详情 | 详情 |
| (XXX) | 54282 | tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetyloxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-[(4-methoxybenzyl)oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | n/a | C46H73NO8SSi | 详情 | 详情 |
| (XXXI) | 54283 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-7-[(4-methoxybenzyl)oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | n/a | C40H63NO7SSi | 详情 | 详情 |
| (XXXII) | 54284 | (4S,7R,8S,9S,16S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-[(4-methoxybenzyl)oxy]-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | n/a | C40H61NO6SSi | 详情 | 详情 |
| (XXXIII) | 43176 | (4S,7R,8S,9S,16S)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C32H53NO5SSi | 详情 | 详情 |