Solid-phase total synthesis of kahalalide A and related analogues.
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.
Bourel-Bonnet
Line
L
School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom.
Rao
Karumanchi V
KV
Hamann
Mark T
MT
Ganesan
A
A
D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D010456:Peptides, Cyclic; C499137:kahalalide A
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