Total synthesis of (-)-salinosporamide A

Yuji Kaiya, Jun Ichi Hasegawa, Takayuki Momose, Takaaki Satou, 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

Fingerprint

Lactams
Arabinose
Scaffolds
Biological Products
Lewis Acids
Carboxylic Acids
Esters
Carbon
Carbohydrates
marizomib

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Medicine(all)

Cite this

Total synthesis of (-)-salinosporamide A. / Kaiya, Yuji; Hasegawa, Jun Ichi; Momose, Takayuki; Satou, Takaaki; Chida, Noritaka.

In: Chemistry - An Asian Journal, Vol. 6, No. 1, 03.01.2011, p. 209-219.

Research output: Contribution to journalArticle

Kaiya, Yuji ; Hasegawa, Jun Ichi ; Momose, Takayuki ; Satou, Takaaki ; Chida, Noritaka. / Total synthesis of (-)-salinosporamide A. In: Chemistry - An Asian Journal. 2011 ; Vol. 6, No. 1. pp. 209-219.
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