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【结 构 式】

【分子编号】32468

【品名】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

【CA登记号】

【 分 子 式 】C34H50N2O5Si

【 分 子 量 】594.86698

【元素组成】C 68.65% H 8.47% N 4.71% O 13.45% Si 4.72%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIX)

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
Extended Information