【结 构 式】 |
【分子编号】48302 【品名】N-(2,2-dimethoxyethyl)-N-(1-formylvinyl)acetamide 【CA登记号】 |
【 分 子 式 】C9H15NO4 【 分 子 量 】201.22244 【元素组成】C 53.72% H 7.51% N 6.96% O 31.8% |
合成路线1
该中间体在本合成路线中的序号:(V)The condensation of 2,2-dimethyl-1,3-dioxan-5-one (I) with aminoacetaldehyde dimethyl acetal (II) followed by acetylation with Ac2O/Et3N afforded the amido dioxin (III). Retro Diels-Alder reaction of dioxin (III) in warm benzonitrile generated the amidoacrolein (V), which was trapped in situ with the silyloxydiene (IV) to yield the cycloadduct (VI). Aldol cyclization between the acetamide and aldehyde functionalities of (VI) in the presence of t-BuOK produced the spiro lactam (VII). Subsequent aldol condensation between the acetal and silyl enolate functions of (VII) under acidic conditions furnished the tricyclic hydroxy ketone (VIII). Reduction of the keto group of (VIII) with NaBH(OAc)3 produced the C-4 axial alcohol (IX). Silylation of both hydroxyl groups of (IX) followed by selective cleavage of the C-2 silyl ether provided the C-4 mono silylated derivative (X). The free C-2 hydroxyl group of (X) was then oxidized to the corresponding ketone (XI) under Swern conditions. The potassium enolate of (XI) was stereoselectively alkylated with p-methoxybenzyl bromide (XII) to yield (XIII). Reduction of the keto group of (XIII) with Red-Al gave rise to the alcohol (XIV) in the undesired equatorial configuration. Inversion of the C-2 stereogenic center of (XIV) was achieved via formation of the sulfonate ester (XVI) with 4-nitrobenzenesulfonyl chloride (XV).
【1】 Maeng, J.-H.; Funk, R.L.; Total synthesis of the immunosuppressant FR901483 via an amidoacrolein cycloaddition. Org Lett 2001, 3, 8, 1125. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 46538 | 2,2-dimethyl-1,3-dioxan-5-one | C6H10O3 | 详情 | 详情 | |
(II) | 34158 | aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine | 22483-09-6 | C4H11NO2 | 详情 | 详情 |
(III) | 48300 | N-(2,2-dimethoxyethyl)-N-(2,2-dimethyl-4H-1,3-dioxin-5-yl)acetamide | C12H21NO5 | 详情 | 详情 | |
(IV) | 48301 | triisopropyl[(1-methylene-2-propenyl)oxy]silane; 1-methylene-2-propenyl triisopropylsilyl ether | C13H26OSi | 详情 | 详情 | |
(V) | 48302 | N-(2,2-dimethoxyethyl)-N-(1-formylvinyl)acetamide | C9H15NO4 | 详情 | 详情 | |
(VI) | 48303 | N-(2,2-dimethoxyethyl)-N-[1-formyl-4-[(triisopropylsilyl)oxy]-3-cyclohexen-1-yl]acetamide | C22H41NO5Si | 详情 | 详情 | |
(VII) | 48304 | 1-(2,2-dimethoxyethyl)-8-[(triisopropylsilyl)oxy]-1-azaspiro[4.5]deca-3,7-dien-2-one | C22H39NO4Si | 详情 | 详情 | |
(VIII) | 48305 | (1S,7R,8R)-7-hydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,9-dione | C11H13NO3 | 详情 | 详情 | |
(IX) | 48306 | (1S,7R,8S,9S)-7,9-dihydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one | C11H15NO3 | 详情 | 详情 | |
(X) | 48307 | (1S,7R,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one | C17H29NO3Si | 详情 | 详情 | |
(XI) | 48308 | (1S,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,7-dione | C17H27NO3Si | 详情 | 详情 | |
(XII) | 27490 | 1-(bromomethyl)-4-methoxybenzene | C8H9BrO | 详情 | 详情 | |
(XIII) | 48309 | (1S,6S,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-2-ene-4,7-dione | C25H35NO4Si | 详情 | 详情 | |
(XIV) | 48310 | (1S,6S,7R,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-4-one | C25H37NO4Si | 详情 | 详情 | |
(XV) | 15809 | 4-nitrobenzenesulfonyl chloride | 98-74-8 | C6H4ClNO4S | 详情 | 详情 |
(XVI) | 48311 | (1S,6S,7R,8S,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-methoxybenzyl)-4-oxo-5-azatricyclo[6.3.1.0(1,5)]dodec-2-en-7-yl 4-nitrobenzenesulfonate | C31H40N2O8SSi | 详情 | 详情 |