Stereocontrolled synthesis of resolvin D1

Abstract

We studied the synthesis of RvD1, a pro-resolving mediator. The intermediate containing vic-diol and enal functional groups was prepared via the oxidation of the γ,δ-epoxy alcohol followed by the epoxide ring opening in one pot. The C11-aldehyde in the resulting enal was converted to the trans iodo-olefin by reaction with TMSC(N₂)Li and subsequent hydrozirconation using in situ generated Cp₂Zr(H)Cl followed by iodination. The trans enynyl alcohol was synthesized by the reaction of the TMS-containing epoxy alcohol with lithium TMS-acetylide. Finally, two fragments were joined by the Sonogashira coupling, and the triple bond was reduced to afford RvD1 stereoselectively.