An enantioselective synthesis of FR182877 provides a chemical rationalization of its structure and affords multigram quantities of its direct precursor

Christopher D. Vanderwal, David A. Vosburg, Sven Weiler, Erik J. Sorensen

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

The evolution of a strategy culminating in an efficient, enantioselective synthesis of the potent microtubule-stabilizing agent FR182877 is described. Guided by a proposed biogenesis of this complex natural product, a solution emerged that involved the first reported example of a double transannular DielsAlder reaction to fashion the key elements of its hexacyclic structure. This pivotal transformation creates a complex pentacycle from a 19-membered macrocyclic pentaene, forming seven new stereogenic centers in a fully diastereocontrolled fashion. The efficiency of the approach ultimately enabled the preparation of multigram quantities of the direct precursor of FR182877 for conversion to the relatively unstable natural product when required. The reactivity of the strained, bridgehead olefin of this secondary metabolite with biologically relevant nucleophiles is also described.

Original languageEnglish (US)
Pages (from-to)5393-5407
Number of pages15
JournalJournal of the American Chemical Society
Volume125
Issue number18
DOIs
StatePublished - May 7 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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