Concise stereocontrolled routes to fumagillol, fumagillin, and TNP-470

David A. Vosburg, Sven Weiler, Erik J. Sorensen

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A concise, diastereoselective synthesis of (±)-fumagillol (3) and formal, enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1) and TNP-470 (2) are reported. The origin of asymmetry is a highly diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone auxiliary. The stereochemical course of a key conjugate addition reaction is controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation.

Original languageEnglish (US)
Pages (from-to)156-166
Number of pages11
JournalChirality
Volume15
Issue number2
DOIs
StatePublished - Feb 10 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Keywords

  • Angiogenesis inhibitors
  • Chiral auxiliary
  • Conjugate addition
  • Diastereo-selective cycloaddition
  • Hetero-Claisen rearrangement
  • Natural products
  • Sharpless epoxidation
  • Total synthesis

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