Synthesis and structural identification of four dihydroxy acids and 11, 12‐leukotriene C4 derived from 11, 12‐leukotriene A4

Abstract

Using a partially purified 12-lipoxygenase from porcine leukocytes, (5Z,8Z,10E,14Z)-12-hydroperoxy-5,8,10,14-icosatetraenoic acid was synthesized from arachidonic acid with a yield of over 35%. The absolute configuration of C-12 was determined as S by chiral-phase column chromatography. It was chemically converted to at least three epoxides with the conjugated triene structure. Two were identified by proton NMR and mass spectrometry to be (5Z,7E, 9E,14Z)-(11S, 12S)-11,12-oxido-5,7,9,14-icosatetraenoic acid (11,12-leukotriene A₄) and (5Z,7Z,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-icosatetraenoic acid (7-cis-11,12-leukotriene A₄). 11,12-Leukotriene A₄ underwent acid hydrolysis to yield two diastereomers of (6E,8E,10E,14Z)-(12S)-5,12-dihydroxy-6,8,10,14-icosatetraenoic acid and two isomers of (14Z)-(12S)-11,12-dihydroxy-5,7,9,14-icosatetraenoic acid. Upon incubation with rat liver glutathione S-transferase, 11,12-leukotriene A₄ was converted to 11,12-leukotriene C₄, a spasmogenic compound.