Hepoxilins B3: Synthesis of all four stereoisomers and a glutathione adduct

✍ Scribed by Yuri Y. Belosludtsev; R.Omindine Kollah; J.R. Falck; Jorge H. Capdevila

• Publisher: Elsevier Science
• Year: 1994
• Tongue: French
• Weight: 300 KB
• Volume: 35
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)73491-5

✦ Synopsis

Abstrack Utilizing (-)quinic acid as a differentiated bii-aldchyde chiron. both pairs of hepoxilin B3 enantiomea'~ and a glutathione mlduct were syntksized by qiosp&fic h&onaliion of an acyclic vtiol. Since its initial isolation in lW9 by Walker et al..1 hepoxilin BJ @Ix&) (1) and related oxiranyl-carbinol.~ have been identified in plants,* marine organisms,~ and several animal species.4 Generally, 1 occurs as a pair of C(lO)-hydroxy diastereomers and, in the case of mammalian tissue, arises from 12(S)hydroperoxyeicosatetraenoic acid [12(S)-HPETE] via enzymatic5 and non-enzymatic intramolecular rearrangement.6 The absolute configuration of 1 isolated from non-mammalian sources is for the most part unknown. In vivo, 1 is rapidly hydrated to the corresponding 10,11.12-trial. txioxilin B3,7 and is a substrate for glutathione S-transferasesS in analogy with other fatty acid epoxides? Arachidonate metabolites from the hepo~xilin pathway have garnered considerable attention recently as a consequence of their varied and potent biological effects. lo As part of a comprehensive synthetic progran+ to expedite the physiologic evaluation and structural elucidation of novel eicosanoids, we report herein a stereocontrolled total synthesis of the four HxB3 stereoisomers 7b,d and lOb,c as well as glutathione conjugate