Solid-phase total synthesis of kahalalide A and related analogues

Bourel-Bonnet, Line, Rao, Karumanchi V., Hamann, Mark T. and Ganesan, A. (2005) Solid-phase total synthesis of kahalalide A and related analogues. Journal of Medicinal Chemistry, 48 (5), 1330-1335. (doi:10.1021/jm049841x).

Record type: Article

Abstract

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.

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Published date: 10 March 2005

Keywords: safety-catch linker, mollusk elysia-rufescens, peptide-synthesis, natural-products, cyclic-peptides, hiv-infection, tuberculosis, depsipeptide, cyclization, cleavage

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