Total synthesis of (+)-amphidinolide A. Assembly of the fragments

Barry M. Trost, Stephen T. Wrobleski, John D. Chisholm, Paul E. Harrington, Michael Jung

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.

Original languageEnglish (US)
Pages (from-to)13589-13597
Number of pages9
JournalJournal of the American Chemical Society
Volume127
Issue number39
DOIs
StatePublished - Oct 5 2005

ASJC Scopus subject areas

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

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