Synthesis and Structure Confirmation Of Compound D, A Proinflammatory Arachidonate Metabolite

✍ Scribed by Dong-Soo Shin; Pendri Yadagiri; J.R. Falck; Jaime L. Masferrer; Michal L. Schwartzman

• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 180 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)99285-2

✦ Synopsis

Summ~ E(5)-and 12(~~-Hydroxyeicosa-5(&3~~,14(Z&ienoic acids @ and S, respectively) and therr 8(B)-analogues were prepared from _Gglutamic acid. Only 4 was comparable by bioassay to natural compound D isolated from comeal epithelium Recently, a novel cytochrome P-450 derived arachidonate metabolite', compound D, was isolated from cornea1 epithelium by Murphy et aLZ and assigned structure & Compound D elicits profound vasodilatory and angiogenic responses and stimulates protein influx into the aqueous humor of the eye*. At present, there remains uncertainty concerning the stereochemistry of the C(12)-alcohol and A**g-olefin due to mechanistic ambiguities in the proposed biosynthesis and to the limited availability of natural material. To clarify the structure and to expedite the biological evaluation of compound D, we report herein the enantiospecific total synthesis of the four stereoisomers implicit in structure 1 and their comparisons by bioassay with natural compound D.