【结 构 式】 |
【分子编号】32470 【品名】benzyl (1S,3S,6S,7S,8S,9S)-9-[[bis(benzyloxy)phosphoryl]oxy]-6-(4-methoxybenzyl)-7-[(triethylsilyl)oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C48H63N2O8PSi 【 分 子 量 】855.096162 【元素组成】C 67.42% H 7.43% N 3.28% O 14.97% P 3.62% Si 3.28% |
合成路线1
该中间体在本合成路线中的序号:(XXI)The sulfonation of the 8(R)-hydroxy group of (XV) with 4-nitrophenylsulfonyl chloride, Et3N and DMAP provides the sulfonate (XVI), which is treated with Tes-OTf and Et3N in dichloromethane to protect the 6-hydroxy group yielding the silyl ether (XVII). The reaction of (XVII) with Cs-OAc and 18-crown-6 in hot benzene gives the 8(S)-acetoxy derivative (XVIII) with inversion of the configuration at the C(8). The reaction of (XVIII) with K2CO3 in methanol gives the corresponding 8(S)-hydroxy compound (XIX), which is treated with diisopropylaminophosphinic acid dibenzyl ester (XX) and tetrazole, and oxidized with tert-butyl hydroperoxide yielding the dibenzyl phosphate ester (XXI). The desilylation of (XXI) with tetrabutylammonium fluoride (TBAF) in THF affords the benzyl protected intermediate (XXII), which is finally debenzylated with H2 over Pd/C in methanol.
【1】 Snider, B.B.; et al.; Total synthesis of (-)-FR901483. J Am Chem Soc 1999, 121, 34, 7778. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
15809 | 4-nitrobenzenesulfonyl chloride | 98-74-8 | C6H4ClNO4S | 详情 | 详情 | |
(XV) | 32464 | benzyl (1S,3S,6S,7S,8R,9R)-7,9-dihydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C28H36N2O5 | 详情 | 详情 | |
(XVI) | 32465 | (1S,3S,6S,7S,8S,9R)-3-[[(benzyloxy)carbonyl](methyl)amino]-7-hydroxy-6-(4-methoxybenzyl)-5-azatricyclo[6.3.1.0(1,5)]dodec-9-yl 4-nitrobenzenesulfonate | C34H39N3O9S | 详情 | 详情 | |
(XVII) | 32466 | (1S,3S,6S,7S,8S,9R)-3-[[(benzyloxy)carbonyl](methyl)amino]-6-(4-methoxybenzyl)-7-[(triethylsilyl)oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-9-yl 4-nitrobenzenesulfonate | C40H53N3O9SSi | 详情 | 详情 | |
(XVIII) | 32467 | (1S,3S,6S,7S,8R,9S)-3-[[(benzyloxy)carbonyl](methyl)amino]-6-(4-methoxybenzyl)-7-[(triethylsilyl)oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-9-yl acetate | C36H52N2O6Si | 详情 | 详情 | |
(XIX) | 32468 | benzyl (1S,3S,6S,7S,8R,9S)-9-hydroxy-6-(4-methoxybenzyl)-7-[(triethylsilyl)oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C34H50N2O5Si | 详情 | 详情 | |
(XX) | 32469 | Diisopropylamidophosphoric acid dibenzyl ester | C20H28NO3P | 详情 | 详情 | |
(XXI) | 32470 | benzyl (1S,3S,6S,7S,8S,9S)-9-[[bis(benzyloxy)phosphoryl]oxy]-6-(4-methoxybenzyl)-7-[(triethylsilyl)oxy]-5-azatricyclo[6.3.1.0(1,5)]dodec-3-yl(methyl)carbamate | C48H63N2O8PSi | 详情 | 详情 | |
(XXII) | 32471 | benzyl (1S,3S,6S,7S,8S,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 |