Total synthesis of (+)-vinblastine: Control of the stereochemistry at C18′

Satoshi Yokoshima, Hidetoshi Tokuyama, Tohru Fukuyama

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

Abstract

Vinblastine has been widely known as a prominent agent in cancer chemotherapy, and in order to search for more potent drugs, various analogs have been derived from natural products. However, because modifications of natural products have limited classes of derivatives, an efficient synthetic route toward vinblastine has been required. Herein a stereocontrolled total synthesis of (+)-vinblastine is described. The synthesis of the upper half features a stereoselective construction of the tertiary alcohol through a 1,3-dipolar cycloaddition of nitrile oxide and a Baeyer-Villiger oxidation, a facile indole formation utilizing a radical cyclization of o-alkenylthioanilide, and a macrocyclization of 2-nitrobenzenesulfonamide. The crucial coupling of the upper half with synthetic vindoline was successfully performed to furnish the coupling product in nearly quantitative yield, and subsequent transformations provided (+)-vinblastine.

Original languageEnglish
Pages (from-to)101-118
Number of pages18
JournalChemical Record
Volume10
Issue number2
DOIs
Publication statusPublished - 2010 Apr 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Chemical Engineering(all)
  • Materials Chemistry

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