Convergent synthesis of leukotriene a methyl ester

✍ Scribed by John G. Gleason; D.Boles Bryan; Charles M. Kinzig

• Publisher: Elsevier Science
• Year: 1980
• Tongue: French
• Weight: 172 KB
• Volume: 21
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)83931-9

✦ Synopsis

A convergent total synthesis of methyl 5,6-oxido-7,9,11,14-eicosapentaenoate from act-2-yn-l-01 and methyl I-formylbutyrate is described. Leukotriene A (1) has been proposed by Samuelsson and his co-workers to be a shortlived intermediate in the arachidonic acid cascade in human and rabbit leukocytesl. This material is believed to play a central role in the conversion of arachidonic acid to leukotrienes, a novel series of 7, 9, 11, 14 eicosatetraenoic acids. Included in this group of metabolites is leukotriene C, suggested by Samuelsson2 to be SRS (slow reacting substance), a potent bronchiospastic agent and mediator of anaphylaxis in human asthma3. Because of our interest in the possible role which these arachidonic acid Arachidonic Acid c I, R=H, Leukotriene A 2, R= CH3 cysteine Leukotriene C (SRS) metabolites may play in respiratory diseases, we have developed a convergent synthesis of the methyl ester 2 of Leukotriene A. An alternate synthesis of 2 was described by Corey and his co-workers subsequent to the completion of this synthesis4.

We envisioned the synthesis of 2 as proceeding via coupling of an y-epoxy-a,$-unsaturated aldehyde 1 to a 2, Z-diene ylide 4. The -