Solid-phase total synthesis of kahalalide A and related analogues

被引:40
作者
Bourel-Bonnet, L
Rao, KV
Hamann, MT
Ganesan, A [1 ]
机构
[1] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England
[2] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA
[3] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA
关键词
D O I
10.1021/jm049841x
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The marine natural product kahalalide A, a cyclic depsipeptide, was prepared by total synthesis on solid-phase. A backbone cyclization strategy was followed, using the Kenner sulfonamide safety-catch linker. By NMR comparison of synthetic and naturally isolated material, the stereochemistry of the methylbutyrate side chain was established as (S). Several analogues were synthesized and tested for antimycobacterial activity. The results indicate that the alcohol functional group in the serine and threonine residues is important, while the methylbutyrate side chain can be replaced by an achiral hexanoate with an increase in activity.
引用
收藏
页码:1330 / 1335
页数:6
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