Total Synthesis of the Polyether Antibiotic Ionomycin

David A. Evans, Robert L. Dow, Thomas L. Shih, James M. Takacs, Robert Zahler

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

A convergent asymmetric synthesis of the calcium ionophore ionomycin has been achieved through a route that is outlined below. The four illustrated subunits, which comprise the C1-C10, C11-C16, C17-C22, and C23-C32 portions of ionomycin, were constructed through the use of chiral enolate bond constructions wherein 9 of the 14 stereogenic centers were created. The remaining chirality at C6, C21, C26, C30, and C31 was incorporated through internal asymmetric induction. In the assemblage process, the ylide derived from the C23-C32 synthon was coupled with the C17-C22 aldehyde. The C23-C26 tetrahydrofuranyl ring and associated C23 stereocenter were then established through intramolecular oxymercuration, which proceeded in a highly diastereoselective manner (≥93:7) with the desired stereochemical outcome. The C16-C17 double bond was constructed through a Julia trans olefination sequence. The union of the C1-C10 keto ester with the assembled C11-C32 aldehyde was achieved through an aldol bond construction. Subsequent oxidation of the C11 alcohol afforded the fully protected ionomycin structure. Final deprotection provided synthetic ionomycin whose absolute configuration is in full agreement with that determined by X-ray crystallography.

Original languageEnglish (US)
Pages (from-to)5290-5313
Number of pages24
JournalJournal of the American Chemical Society
Volume112
Issue number13
DOIs
StatePublished - Jan 1990

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Ionomycin
Polyethers
Antibiotics
Aldehydes
Ionophores
Anti-Bacterial Agents
Chirality
X ray crystallography
Calcium
Esters
Alcohols
Oxidation
Calcium Ionophores
X Ray Crystallography

ASJC Scopus subject areas

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

Cite this

Total Synthesis of the Polyether Antibiotic Ionomycin. / Evans, David A.; Dow, Robert L.; Shih, Thomas L.; Takacs, James M.; Zahler, Robert.

In: Journal of the American Chemical Society, Vol. 112, No. 13, 01.1990, p. 5290-5313.

Research output: Contribution to journalArticle

Evans, David A. ; Dow, Robert L. ; Shih, Thomas L. ; Takacs, James M. ; Zahler, Robert. / Total Synthesis of the Polyether Antibiotic Ionomycin. In: Journal of the American Chemical Society. 1990 ; Vol. 112, No. 13. pp. 5290-5313.
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