Simple efficient synthesis of LTB4 and 12-epi-LTB4

✍ Scribed by Robert Zamboni; Joshua Rokach

• Publisher: Elsevier Science
• Year: 1982
• Tongue: French
• Weight: 189 KB
• Volume: 23
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)87415-8

✦ Synopsis

llsing L-and II-arabinose respectively as the source of chirality at C-12 in LTR,, efficient new syntheses of LTR, and 12-epi-LTR, have been realized. LTR,, a metabolite of arachidonic acid, has recently been isolated and characterized.' The biological activity of LTQ2 (potent chemotactic and chemokinetic properties and induction of vascular permeablity) and the availability of only ug quantities from biological sources has resulted in the synthesis of this important mediator of allergic and inflammatory states.3*4 In our first synthesis of LTR, la4 (Scheme 2) -2-deoxy n-ribose was used in a chirally economic manner to provide the two synthons ;! and Ab which were coupled to yield the natural product. The present approach, which is also entirely stereospecific in nature, was designed to allow more flexibility and versatility in our overall approach to the synthesis of metabolites of arachidonic acid and some of their isomers. This strategy is illustrated below for the synthesis of LTR, & (natural isomer) and l?-epi LTR, E. The selection of lb as target molecule was dictated by our -desire to investigate the pharmacology, biochemistry and receptor binding properties of this isomer of LTR, in which the only difference with the natural product is the stereochemistry at carbon 12. Our plan was to develop stereospecific routes to hoth R and S isomers of 4 -* The two compounds could then be combined with z4 through an appropriate 4 carbon unit to form the desired LTR, isomers la and lb. --Retrosynthetic analysis for Synthon 4a (Scheme 1) shows that L-arabinose 3 is an appropriate starting material. _-SCHEME 1 4a R*=H, R2=ot-RoPsi 4_b Rs=Ot-WPSi, Q=H ?631