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

作者：Shigeto Kitamura, Takao Shimizu, Ichiro Miki, Takashi Izumi, Takeshi Kasama, Akira Sato, Hiroshi Sano, Yousuke Seyama · 发表于：European Journal of Biochemistry · 年份：1988 · DOI：10.1111/j.1432-1033.1988.tb14336.x · 被引用次数：20 · 研究领域：Eicosanoids and Hypertension Pharmacology、Inflammatory mediators and NSAID effects、Genomics, phytochemicals, and oxidative stress

Using a partially purified 12-lipoxygenase from porcine leukocytes, (5Z,8Z,10E,14Z)-12-hydroperoxy-5,8,10,14-icosate traenoic 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-ic osatetraenoic acid (11,12-leukotriene A4) and (5Z,7Z,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-ic osatetraenoic 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-i cosatetraenoic 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.