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

Jonathan J. Duffield, George Pettit

Research output: Contribution to journalArticle

15 Citations (Scopus)

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

Fingerprint

diastereomers
synthesis
acids
Depsipeptides
Oxazolidinones
Chirality
Cell growth
Cobalt
Aldehydes
Lactic Acid
cobalt
Salts
aldehydes
lactates
cell growth
Growth
salts
dolatrienoic acid
Neoplasms
tiglic acid

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid. / Duffield, Jonathan J.; Pettit, George.

In: Journal of Natural Products, Vol. 64, No. 4, 04.2001, p. 472-479.

Research output: Contribution to journalArticle

Duffield, Jonathan J. ; Pettit, George. / Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid. In: Journal of Natural Products. 2001 ; Vol. 64, No. 4. pp. 472-479.
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