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【结 构 式】 
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【分子编号】49273 【品名】3-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]propanal 【CA登记号】 |
【 分 子 式 】C21H35NO3SSi 【 分 子 量 】409.66534 【元素组成】C 61.57% H 8.61% N 3.42% O 11.72% S 7.83% Si 6.86% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The reduction of the methyl ester of (XVI) with DIBAL in dichloromethane gives the aldehyde (XVIII), which is condensed with the chiral phosphonate (XIX) by means of BuLi in ethyl ether to yield the enoylsultam (XX). The methylation of (XX) with L-selectride and methyl iodide affords the methylated sultam (XXI), which is desilylated with TBAF and reprotected with Tes-Cl and TEA to provide triethylsilyl ether (XXII) with a more favorable silyl leaving group needed in the remaining synthetic steps. Elimination of the sultam group of (XXII) by means of DIBAL in dichloromethane gives the aldehyde (XXIII), which is condensed with the ketone (XXIV) by means of LDA to yield the aldol (XXV). The protection of the OH group of (XXV) with Troc-Cl ad pyridine affords compound (XXVI), which is oxidized at the terminal vinyl group by means of OsO4 and NaIO4 to provide the aldehyde (XXVII). The selective desilylation of (XXVII) by means of HF and pyridine furnishes the hydroxy aldehyde (XXVIII).
| 【1】 Martin, H.J.; et al.; How stable are epoxides? A novel synthesis of epothilone B. Angew Chem. Int Ed Engl 2000, 39, 3, 581. |
| 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) | 49271 | methyl 3-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]propanoate | C22H37NO4SSi | 详情 | 详情 | |
| (XVIII) | 49273 | 3-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]propanal | C21H35NO3SSi | 详情 | 详情 | |
| (XIX) | 49274 | diethyl 2-(10,10-dimethyl-2,2-dioxo-2lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]dec-4-yl)-2-oxoethylphosphonate | C16H28NO6PS | 详情 | 详情 | |
| (XX) | 49275 | 4-((E)-5-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]-2-pentenoyl)-10,10-dimethyl-2lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-2,2-dione | C33H52N2O5S2Si | 详情 | 详情 | |
| (XXI) | 49276 | 4-((2S)-5-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]-2-methylpentanoyl)-10,10-dimethyl-2lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-2,2-dione | C34H56N2O5S2Si | 详情 | 详情 | |
| (XXII) | 49277 | 10,10-dimethyl-4-[(2S)-2-methyl-5-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)pentanoyl]-2lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-2,2-dione | C34H56N2O5S2Si | 详情 | 详情 | |
| (XXIII) | 49278 | (2S)-2-methyl-5-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)pentanal | C24H41NO3SSi | 详情 | 详情 | |
| (XXIV) | 44451 | (5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one | C16H32O2Si | 详情 | 详情 | |
| (XXV) | 49279 | (4S,7R,8R,9S)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-5,5,7,9-tetramethyl-12-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)-1-dodecen-6-one | C40H73NO5SSi2 | 详情 | 详情 | |
| (XXVI) | 49280 | (1R,2R,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,4,4-trimethyl-1-[(1S)-1-methyl-4-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)butyl]-3-oxo-7-octenyl 2,2,2-trichloroethyl carbonate | C43H74Cl3NO7SSi2 | 详情 | 详情 | |
| (XXVII) | 49281 | (1R,2R,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,4,4-trimethyl-1-[(1S)-1-methyl-4-((2R,3S)-2-methyl-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)butyl]-3,7-dioxoheptyl 2,2,2-trichloroethyl carbonate | C42H72Cl3NO8SSi2 | 详情 | 详情 | |
| (XXVIII) | 49282 | (1R,2R,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-1-((1S)-4-[(2R,3S)-3-[(2S,3E)-2-hydroxy-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]-1-methylbutyl)-2,4,4-trimethyl-3,7-dioxoheptyl 2,2,2-trichloroethyl carbonate | C36H58Cl3NO8SSi | 详情 | 详情 |