Toward the total synthesis of onchidin, a cytotoxic cyclic depsipeptide from a mollusc

Shu Kobayashi, Jun Kobayashi, Ryo Yazaki, Masaharu Ueno

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Abstract

The total synthesis of onchidin (1), a cytotoxic, C2-symmetric cyclic decadepsipeptide from a marine mollusc, according to the published structure, is described. A novel β-amino acid, (2S,3S)-3-amino-2-methyl-7- octynoic acid (AMO), was efficiently prepared in high yield with high diastereo- and enantioselectivity based on a catalytic asymmetric three-component Mannich-type reaction with a chiral zirconium catalyst. The formation of sterically unfavorable N-methyl amide and hindered ester bonds were successfully demonstrated, and final macrocyclization was achieved at a secondary-amide site. Completion of the synthesis of 1 suggested that a revision of the structure of the natural product is required. Two diastereomers were also synthesized as candidates for the actual structure of onchidin. Furthermore, efficient solid-phase methods were employed for the combinatorial synthesis of other derivatives to clarify the real structure of onchidin. The solid-phase assembly of a pentadepsipeptide containing all the building blocks was established followed by dimeric cyclization in solution.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalChemistry - An Asian Journal
Volume2
Issue number1
DOIs
Publication statusPublished - Jan 24 2007
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry

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