（+）-负霉素的不对称合成。

Asymmetric synthesis of (+)-negamycin.

作者信息

Jain Rajendra P, Williams Robert M

机构信息

Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.

出版信息

J Org Chem. 2002 Sep 6;67(18):6361-5. doi: 10.1021/jo025636i.

DOI:10.1021/jo025636i

PMID:12201754

Abstract

An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into beta-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps.

摘要

以市售的(5R,6S)-4-(苄氧羰基)-5,6-二苯基-2,3,5,6-四氢-4H-1,4-恶嗪-2-酮(2)为起始原料，实现了抗生素(+)-负霉素(1)的不对称合成。该合成过程包括对2的内酯羰基进行稳定化维蒂希烯化反应，随后进行不对称氢化反应，以优异的非对映选择性生成相应的全顺式恶嗪4。将4转化为β-烷氧基亚胺7，随后在CeCl3促进下对7进行螯合控制的烯丙基化反应，以良好的非对映选择性生成相应的高烯丙基胺8，经11步反应，8以25%的总收率顺利转化为(+)-负霉素(1)。