Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid

Jonathan J. Duffield, George Pettit

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The stereospecific synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acids (2) was achieved using an approach consisting of 16 linear steps. The C-11-C-16 unit was prepared in seven steps from ethyl (S)lactate and coupled using a trans-selective Wittig - Schlosser reaction to the C-7-C-10 fragment. Chirality at the C-7 position was introduced using an Evan's-type chiral auxiliary in a cobalt-mediated Reformatsky reaction to give the (3S,11S)-aldehyde 24. Subsequent Wittig reaction with a phosphonium salt derived in three steps from tiglic acid gave (7S,15S)-dolatrienoic acid, one of the four possible diastereoisomers of the nonpeptide portion of the strong Cancer cell growth inhibitory cyclodepsipeptide dolastatin 14 (1). A second diastereoisomer, (7R,15S)-dolatrienoic acid, was synthesized employing chiral oxazolidinone 21 by an analogous synthetic route.

Original languageEnglish (US)
Pages (from-to)472-479
Number of pages8
JournalJournal of Natural Products
Volume64
Issue number4
DOIs
StatePublished - Apr 2001

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid'. Together they form a unique fingerprint.

Cite this