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.

On the structure and synthesis of neuroprotectin D1, a novel anti-inflammatory compound of the docosahexaenoic acid family

“…2B, C). Importantly, the value of J 13,14 was found to be ‫,01ف‬ which is indicative of cis-geometry of the vinyl group, whereas J 11,12 and J 15,16 were ‫,51ف‬ clear evidence of the trans-nature of the C11-C12 and C15-C16 bonds (Scheme 1).…”

“…3. In agreement with our one-dimensional 1 H-NMR observations, it was apparent that 10,17(S)-diHDHA did not have a conjugated E,E-diene fragment in it, as it would have produced a resonance with a chemical shift ␦ of 6.15-6.24 ppm that is seen, for example, in all-trans isomers of 9(S)-and 13(S)-hydroxylinoleyl alcohols (9), 9(S)-and 13(S)-hydroxymonolinoleoyl glycerols (10), 5,6-dihydroxyeicosapenta-7E,9E,11Z,14Z,17Z-enoic acid (11), 5-oxo-eicosatetra-7E,9E,11Z,14Z-enoic acid (12), 14,15-dihydroxyeicosatetra-5Z,8Z,10E,12E-enoic acid (13), and 5,12(S)-dihydroxyeicosatetra-6E,8E,10E-enoic acid (14). Generally, a proton system similar to the 11E,13E,15Z conjugated triene would have produced at least six distinctive groups of signals of olefinic protons (13), whereas ptLOX-synthesized 10,17(S)-diHDHA gave only four (Figs.…”

A one-step method of 10,17-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid synthesis by soybean lipoxygenase

“…The spectrum lacked a proton resonance with d 6.15-6.24 ppm, which would have been present if the compound had a conjugated 11E,13E or 13E,15E fragment. Such resonances have been reported for several compounds with conjugated E,E double bonds, for example, all-trans isomers of 9(S)-and 13(S)-hydroxy linoleyl alcohols (14), 9(S)-and 13(S)-hydroxy monolinoleoyl glycerols (15), 5, 6-dihydroxyeicosapenta-7E,9E,11Z,14Z,17Z-enoic acid (16), 5-ketoeicosatetra-7E,9E,11Z,14Z-enoic acid (17), 14,15-dihydroxyeicosatetra-5Z,8Z,10E,12E-enoic acid (18), and 5,12 (S)-dihydroxyeicosatetra-6E,8E,10E-enoic acid (19).…”