Biomimetic synthesis of leukotriene A

✍ Scribed by Vince Atrache; Jin-Keon Pai; Dai-Eun Sok; Charles J. Sih

• Publisher: Elsevier Science
• Year: 1981
• Tongue: French
• Weight: 275 KB
• Volume: 22
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)81927-4

✦ Synopsis

A bioqenetically patterned conversion of 1 into 2 is described. This transformation has been found to be non-stereospecific with respect to the geometry of the newly qenerated double bond at C-9(10). Leukotriene A (LTA), S(S)-trans-5,6-oxido-7,9-E-11,14-Z-eicosatetraenoic acid1 was shown to he an unstahle pivotal biosynthetic precursor of leukotriene 62 (LTR), 5(S),12-(R)-dihydroxy-6,14-L-8,10-E-eicosatetraenoic acid3 and the slow reactinq suhstances4 [SRS-GSH (LTC), SRS-Cys-Gly (LTD) and SRS-Cys (LTE)]. In turn, LTA5 is enzymically derived from arachidonic acid via the intermedlate , 5(S)-h.ydroperoxy-6-l_8-8,11,14-L-eicosatetraenoic acid C(S)-5-HPETE]. Recently, we developed a biomimetic conversion6 of (+)5-HPETE methyl ester7 (L) into (?)LTA methvl ester c), a key chemical intermediate in the syntheslsIy8 of slow reacting substances. This method entailed the conversion of Lto its mesylate, 3 and the selective abstraction of a -C-10 proton by a hindered base to afford 2.