Synthesis of epoxyeicosatrienoic acids and heteroatom analogs

J. R. Falck, P. Yadagiri, J. Capdevila

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The chapter presents a study on synthesis of epoxyeicosatrienoic acids and heteroatom analogs. The chapter mentions the need for a comprehensive review of the current status of the epoxygenase pathway with a critical discussion of its implications. The most characteristic and extensively studied epoxygenase metabolites are the four regioisomeric cis-epoxyeicosatrienoic acids (EETs). They are relatively stable to hydrolysis at physiological pH [for example, leukotriene A4 (LTA4) and hepoxilin A3]. The exception is 5,6-EET which, in its free-acid form, readily decomposes to 5,6-dihydroxyeicosatrienoic acid and/or the corresponding δ-1actone. The absolute configuration of the EETs has been determined using material obtained from in vitro incubation of arachidonic acid with the major phenobarbital-inducible form of rat liver microsomal cytochrome P-450. Recent results suggest that the enantiomeric composition is highly dependent on the identity of the cytochrome P-450 isozyme. This may be significant because in some instances biological activity is sensitive to EET stereochemistry. Chiral syntheses of all the EET enantiomers have been achieved. Most investigators have relied on racemic EETs prepared by Corey's site-specific oxidation methodology or, more conveniently, by nonselective peracid epoxidation of arachidonic acid. This chapter describes procedures based on the latter reaction that have proved reliable in laboratories for the production and purification of nanomole-millimole amounts of EETs and their methyl esters. In light of the increasing interest in EET heteroatom analogs, protocols for converting EETs to cis-thiiranes and cis-aziridines are also included.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalMethods in Enzymology
Volume187
Issue numberC
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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