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【结 构 式】 
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【分子编号】46184 【品名】tert-butyl(dimethyl)silyl (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentyl ether; 4-[(E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-butenyl]-2-methyl-1,3-thiazole 【CA登记号】 |
【 分 子 式 】C33H63NO4SSi2 【 分 子 量 】626.10456 【元素组成】C 63.31% H 10.14% N 2.24% O 10.22% S 5.12% Si 8.97% |
合成路线1
该中间体在本合成路线中的序号：(XXX)Assembly of the target compound: The condensation of the phosphonium salt (VII) with the aldehyde (XV) by means of NaHMDS in THF gives the adduct (XIX), which is debenzylated and hydrogenated with H2 over Pd/Al2O3 in ethanol and oxidized with NaIO4 and RuCl3 to yield the carboxylic acid (XX). The activation of (XX) with pivaloyl chloride affords the anhydride (XXI), which is condensed with the lithium oxazolidinone (XXII) to provide the cyclic amide (XXIII). The enantioselective hydroxylation of (XXIII) by means of the Davis oxaziridine and NaHMDS gives the alpha-hydroxyamide (XXIV), which is treated with N,O-dimethylhydroxylamine (XXV) to yield the methoxyamide (XXVI). The protection of the OH group of (XXVI) with Tbdms-OTf and lutidine affords the silyl ether (XXVII), which is treated with MeLi in THF, affording the methyl ketone (XXVIII). The condensation of (XXVIII) with tributyl(2-methylthiazol-4-ylmethyl)phosphonium chloride (XXIX) by means of KHMDS in THF provides the adduct (XXX).
| 【1】 Mulzer, J.; et al.; A novel highly stereoselective total synthesis of epothilone B and of its (12R,13R) acetonide. Tetrahedron Lett 2000, 41, 40, 7635. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 46168 | ((3S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methylbutyl)(triphenyl)phosphonium iodide | C29H40IOPSi | 详情 | 详情 | |
| (XV) | 46175 | (4S,5R)-5-[3-(benzyloxy)propyl]-2,2,4-trimethyl-1,3-dioxolane-4-carbaldehyde | C17H24O4 | 详情 | 详情 | |
| (XIX) | 46176 | benzyl 3-[(4R,5R)-5-((E,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-1-pentenyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]propyl ether; [((2S,4E)-5-[(4R,5R)-5-[3-(benzyloxy)propyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methyl-4-pentenyl)oxy](tert-butyl)dimethylsilane | C28H48O4Si | 详情 | 详情 | |
| (XX) | 46177 | 3-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]propionic acid | C21H42O5Si | 详情 | 详情 | |
| (XXI) | 46178 | 2-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]propionic 1,1-dimethylpropionic anhydride | C26H50O6Si | 详情 | 详情 | |
| (XXII) | 46185 | [(4S,5R)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]lithium | C10H10LiNO2 | 详情 | 详情 | |
| (XXIII) | 46179 | (4S,5R)-3-[3-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one | C31H51NO6Si | 详情 | 详情 | |
| (XXIV) | 46180 | (4S,5R)-3-[(2S)-3-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-hydroxypropanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one | C31H51NO7Si | 详情 | 详情 | |
| (XXV) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (XXVI) | 46181 | (2S)-3-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-hydroxy-N-methoxy-N-methylpropanamide | C23H47NO6Si | 详情 | 详情 | |
| (XXVII) | 46182 | (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-N-methoxy-N-methylpropanamide | C29H61NO6Si2 | 详情 | 详情 | |
| (XXVIII) | 46183 | (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-butanone | C28H58O5Si2 | 详情 | 详情 | |
| (XXIX) | 40820 | tributyl[(2-methyl-1,3-thiazol-4-yl)methyl]phosphonium chloride | C17H33ClNPS | 详情 | 详情 | |
| (XXX) | 46184 | tert-butyl(dimethyl)silyl (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentyl ether; 4-[(E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-butenyl]-2-methyl-1,3-thiazole | C33H63NO4SSi2 | 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 selective deprotection of (XXX) with CSA in dichloromethane gives the primary alcohol (XXXI), which is oxidized with DMP in dichloromethane to yield the aldehyde (XXXII). The condensation of (XXXII) with methyltriphenylphosphonium iodide (XXXIII) by means of BuLi in hexane/THF, followed by treatment with HCl in ethanol, affords the diunsaturated vicinal diol (XXXIV), which is selectively silylated to provide the vicinal diol (XXXV). The monosulfonation of (XXXV) with Ms-Cl and TEA furnishes the mesylate (XXXVI), which is cyclized to the epoxide (XXXVII) by means of K2CO3 in methanol. The oxidation of the terminal double bond of (XXXVII) with OsO4 and NaIO4 gives the aldehyde (XXXVIII), which is condensed with the intermediate ketone (XVIII) by means of LDA in THF to provide the adduct (XXXIX).
| 【1】 Mulzer, J.; et al.; A novel highly stereoselective total synthesis of epothilone B and of its (12R,13R) acetonide. Tetrahedron Lett 2000, 41, 40, 7635. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIIII) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (XVIII) | 44451 | (5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one | C16H32O2Si | 详情 | 详情 | |
| (XXX) | 46184 | tert-butyl(dimethyl)silyl (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentyl ether; 4-[(E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-butenyl]-2-methyl-1,3-thiazole | C33H63NO4SSi2 | 详情 | 详情 | |
| (XXXI) | 46186 | (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-pentanol | C27H49NO4SSi | 详情 | 详情 | |
| (XXXII) | 46187 | (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentanal | C27H47NO4SSi | 详情 | 详情 | |
| (XXXIV) | 46188 | (1E,3S,5R,6R,10S)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,11-dodecadiene-3,5,6-triol | C19H31NO3S | 详情 | 详情 | |
| (XXXV) | 46189 | (1E,3S,5R,6R,10S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,11-dodecadiene-5,6-diol | C25H45NO3SSi | 详情 | 详情 | |
| (XXXVI) | 46190 | (1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate | C26H47NO5S2Si | 详情 | 详情 | |
| (XXXVII) | 46191 | tert-butyl(dimethyl)silyl (1S,2E)-2-methyl-1-([(2S,3R)-3-methyl-3-[(4S)-4-methyl-5-hexenyl]oxiranyl]methyl)-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-4-[(2S,3R)-3-methyl-3-[(4S)-4-methyl-5-hexenyl]oxiranyl]-1-butenyl)-2-methyl-1,3-thiazole | C25H43NO2SSi | 详情 | 详情 | |
| (XXXVIII) | 46192 | (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-methylpentanal | C24H41NO3SSi | 详情 | 详情 | |
| (XXXIX) | 46193 | (4S,7R,8S,9S)-4-[[tert-butyl(dimethyl)silyl]oxy]-12-[(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]-8-hydroxy-5,5,7,9-tetramethyl-1-dodecen-6-one | C40H73NO5SSi2 | 详情 | 详情 |