Synthesis and structural identification of four dihydroxy acids and 11,12-leukotriene C4 derived from 11,12-leukotriene A4.
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.
Kitamura
S
S
Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo, Japan.
Shimizu
T
T
Miki
I
I
Izumi
T
T
Kasama
T
T
Sato
A
A
Sano
H
H
Seyama
Y
Y
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood*; D001091:Arachidonate Lipoxygenases / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D007962:Leukocytes / Q000201:enzymology*; D017572:Leukotriene A4 / Q000031:analogs & derivatives*; D015289:Leukotrienes / Q000096:biosynthesis / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013189:SRS-A / Q000302:isolation & purification*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D017572:Leukotriene A4; D015289:Leukotrienes; D013189:SRS-A; C021201:12-HPETE; C051889:11,12-leukotriene A4; D001091:Arachidonate Lipoxygenases; D001092:Arachidonate 12-Lipoxygenase