Total synthesis of (-)-salinosporamide A

Yuji Kaiya, Jun Ichi Hasegawa, Takayuki Momose, Takaaki Sato, Noritaka Chida

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A detailed description of our second-generation total synthesis of salinosporamideA is presented. Three contiguous stereocenters in the γ-lactam structure seen in the natural product were established by stereoselective functionalization of a D-arabinose scaffold, including an Overman rearrangement to generate a highly congested tetrasubstituted carbon center. One of the definitive reactions in the synthesis was a Lewis acid mediated skeletal rearrangement of a pyranose structure, which enabled the practical conversion of the carbohydrate scaffold to the γ-lactam structure embedded in salinosporamideA. The use of a benzyl ester as a protective group for a sterically hindered carboxylic acid led to a one-pot global deprotection at the end of the synthesis. Rearrange your chemistry! The total synthesis of anticancer natural product salinosporamideA has been achieved through a unique skeletal rearrangement (see scheme). This reaction enabled the construction of the densely functionalized γ-lactam structure found in salinosporamideA through practical methodologies including an Overman rearrangement on a D-arabinose scaffold.

Original languageEnglish
Pages (from-to)209-219
Number of pages11
JournalChemistry - An Asian Journal
Volume6
Issue number1
DOIs
Publication statusPublished - 2011 Jan 3

Keywords

  • carbohydrates
  • inhibitors
  • natural products
  • rearrangement
  • total synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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