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【结 构 式】 
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【分子编号】43447 【品名】2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl((2R,5R,6S,7R)-2-(benzyloxy)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-6-methyloctanoyl)carbamate 【CA登记号】 |
【 分 子 式 】C48H85NO14Si3 【 分 子 量 】984.45774 【元素组成】C 58.56% H 8.7% N 1.42% O 22.75% Si 8.56% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The Curtius degradation of carboxylic acid (XIV) with Ph2PON3 and 2-(trimethylsilyl)ethanol (A) gives the carbamate (XV), which is acylated with 2-(benzyloxy)acetyl chloride (XVI) and LiHMDS in THF, yielding the imide (XVII). The condensation of (XVII) with aldehyde (XVIII) by means of TiCl4 and DIEA in dichloromethane affords the expected adduct (XIX), which is oxidized with TFAA and DMSO in dichloromethane/DIEA, providing the beta-ketoimide (XX) as a diastereomeric mixture at the benzyloxy group. The cyclization of (XX) by means of CSA in methanol, followed by separation of the diastereomeric mixture, furnished the hydroxy tetrahydropyran derivative (XXI), which is submitted to a Swern oxidation to give the trahydropyranone (XXII). The reaction of (XXII) with diiodomethane, TiCl4 and Zn yields the exo-methylene compound (XXIII), which is desilylated with TBAF in DMF to afford intermediate (XXIV). Finally, this compound is submitted to a reductive cleavage of the benzyloxy and cyclic carbonate groups with Na/NH3 in THF/ethyl ether to furnish the target compound.
| 【1】 Roush, W.R.; Pfeifer, L.A.; Total synthesis of mycalamide A and 7-epi-mycalamide A. Org Lett 2000, 2, 6, 859. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 20323 | 2-(trimethylsilyl)-1-ethanol | 2916-68-9 | C5H14OSi | 详情 | 详情 |
| (XIV) | 43443 | (4S,4aR,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxine-4-carboxylic acid | C15H22O9 | 详情 | 详情 | |
| (XV) | 43444 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-ylcarbamate | C20H35NO9Si | 详情 | 详情 | |
| (XVI) | 10493 | 2-(Benzyloxy)acetyl chloride; Benzyloxyacetyl chloride | 19810-31-2 | C9H9ClO2 | 详情 | 详情 |
| (XVII) | 43445 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl[2-(benzyloxy)acetyl]carbamate | C29H43NO11Si | 详情 | 详情 | |
| (XVIII) | 43446 | (3R,4S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methylhexanal | C19H42O3Si2 | 详情 | 详情 | |
| (XIX) | 43447 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl((2R,5R,6S,7R)-2-(benzyloxy)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-6-methyloctanoyl)carbamate | C48H85NO14Si3 | 详情 | 详情 | |
| (XX) | 43448 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl((5R,6S,7R)-2-(benzyloxy)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-3-oxooctanoyl)carbamate | C48H83NO14Si3 | 详情 | 详情 | |
| (XXI) | 43449 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl[(2S)-2-(benzyloxy)-2-[(2R,4R,5R,6R)-4-hydroxy-2-methoxy-5,6-dimethyltetrahydro-2H-pyran-2-yl]ethanoyl]ca | C37H57NO14Si | 详情 | 详情 | |
| (XXII) | 43450 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl[(2S)-2-(benzyloxy)-2-[(2R,5S,6R)-2-methoxy-5,6-dimethyl-4-oxotetrahydro-2H-pyran-2-yl]ethanoyl]carbamate | C37H55NO14Si | 详情 | 详情 | |
| (XXIII) | 43451 | 2-(trimethylsilyl)ethyl (4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl[(2S)-2-(benzyloxy)-2-[(2R,5R,6R)-2-methoxy-5,6-dimethyl-4-methylenetetrahydro-2H-pyran-2-yl]ethanoyl]car | C38H57NO13Si | 详情 | 详情 | |
| (XXIV) | 43452 | (2S)-N-((4S,4aS,6R,8S,8aR)-8-methoxy-7,7-dimethyl-6-[[(4S)-2-oxo-1,3-dioxolan-4-yl]methyl]hexahydropyrano[3,2-d][1,3]dioxin-4-yl)-2-(benzyloxy)-2-[(2R,5R,6R)-2-methoxy-5,6-dimethyl-4-methylenetetrahydro-2H-pyran-2-yl]ethanamide | C32H45NO11 | 详情 | 详情 |