Stereospecific synthesis of two metabolites of LTB4

✍ Scribed by Robert Zamboni; Joshua Rokach

• Publisher: Elsevier Science
• Year: 1982
• Tongue: French
• Weight: 219 KB
• Volume: 23
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)85704-4

✦ Synopsis

The stereospecific synthesis of the recently identified metabolites of LT8 1: 5(S),lZ(R),20-trihydroxy-6-cis,8,10-trans,l4-cis-eicosatetraenoic acid 2 and 5(S),12!Rr,dihydroxy-6-cis,8,10-trans,l4-cis-eicosatetraen-l,20-dioic acid 3, via thz synthon 4 has been accomplished; identity of synthetic and natural products has 6een confirmed. LTB, is a member of the arachidonic acid cascade recently identified by Borgeat and Samuelsson. 1 Arachidonic acid is transformed via the enzyme 5-lipoxygenase to 5-HPETE which in turn is transformed via a dehydrase step to LTA,. LTA, is then diverted to two main pathways: action of glutathione transferase on LTA, leads to LTC,, 0, and E,, components of the so-called slow reacting substances of anaphylaxis SRS-A. The other major known metabolitic transformation of LTA, is the enzymatic hydration to yield LTB,. LTB, is a potent chemotactic agent and its implication in inflammatory processes is very likely and is being actively investigated.* The detailed metabolitic transformation of LTB, has not yet been elucidated. Preliminary reports have, however, identified two primary metabolites of LTB, namely, whydroxy LTB, 1 3s4 and w-carboxy LTB, z.4 ;m&" ;mO*H 1 LTl34 2 R,CH,OH 3_ R=CO,H k SE1 SEt 4_ 5_ We have recently reported two stereospecific syntheses of LT8, and isomers5~6 and we wish to describe now the first synthesis, completely stereospecific in nature, of metabolites