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【结 构 式】 
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【分子编号】48321 【品名】benzyl (1S,3S,6S,7S,8S,9S)-7,9-dihydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C28H36N2O5 【 分 子 量 】480.60432 【元素组成】C 69.98% H 7.55% N 5.83% O 16.65% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)Methylation of the carbamate nitrogen atom of (XXIV) by means of iodomethane and NaH produced (XXV). Subsequent cleavage of the silyl ether group of (XXV) with HF gave diol (XXVI). The selective phosphitylation of the C-4 hydroxyl group of (XXVI), followed by oxidation of the resulting phosphite ester (XXVII) with m-chloroperbenzoic acid in the presence of Et3N, furnished phosphate (XXVIII). Finally, hydrogenolysis of the dibenzyl phosphate and benzyl carbamate functionalities of (XXVIII) provided the title compound, which was isolated as the hydrochloride salt.
| 【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 |
|---|---|---|---|---|---|---|
| (XXIV) | 48319 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-ylcarbamate | C33H48N2O5Si | 详情 | 详情 | |
| (XXV) | 48320 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C34H50N2O5Si | 详情 | 详情 | |
| (XXVI) | 48321 | benzyl (1S,3S,6S,7S,8S,9S)-7,9-dihydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C28H36N2O5 | 详情 | 详情 | |
| (XXVII) | 48322 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[bis(benzyloxy)phosphino]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C42H49N2O7P | 详情 | 详情 | |
| (XXVIII) | 48323 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[bis(benzyloxy)phosphoryl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C42H49N2O8P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XX)The methylation of the carbamate NH group of (XVIII) with Me-I and NaH in DMF gives the corresponding N-methyl derivative (XIX), which is desilylated by means of HF in acetonitrile to yield the axial alcohol (XX). The selective esterification of (XX) with (BnO)2P-N(iPr)2 (XXI), followed by oxidation with MCPBA and TEA, affords the dibenzyl hydrogen phosphate (XXII), which is finally deprotected by hydrogenation with H2 over Pd/C in ethanol to furnish the target FR-901483.
| 【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 |
|---|---|---|---|---|---|---|
| (XVIII) | 48319 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-ylcarbamate | C33H48N2O5Si | 详情 | 详情 | |
| (XIX) | 48320 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C34H50N2O5Si | 详情 | 详情 | |
| (XX) | 48321 | benzyl (1S,3S,6S,7S,8S,9S)-7,9-dihydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C28H36N2O5 | 详情 | 详情 | |
| (XXI) | 40539 | N-[bis(phenylmethoxy)phosphanyl]-N-propan-2-ylpropan-2-amine; bis(benzyloxy)phosphino-diisopropyl-amine | 108549-23-1 | C20H28NO2P | 详情 | 详情 |
| (XXII) | 48323 | benzyl (1S,3S,6S,7S,8R,9S)-9-[[bis(benzyloxy)phosphoryl]oxy]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C42H49N2O8P | 详情 | 详情 |