Synthesis of Resolvin D6 and the Silyl Ether of the Resolvin E2 Methyl Ester via trans -Enynyl Alcohols

Abstract

Two trans -enynyl alcohol intermediates corresponding to the C1-C8 and C13-C22 parts of resolvin D6 (RvD6) were prepared through the Hudrlik-Peterson reaction of the TMS-substituted trans -epoxy alcohols with TMS-acetylide and subsequent TMS-desilylation. These intermediates were coupled with a 1,4-dihalo-2-butyne derivative under copper catalysis, and the resulting acetylene was reduced with Zn(Cu/Ag) to afford the TBS ether of RvD6 methyl ester. Desilylation with TBAF yielded the γ-lactone of RvD6, which was hydrolyzed to RvD6. The total yield of RvD6 was 1.9% in 19 steps from (3-trimethylsilyl)propargyl alcohol. The TBS ether of RvE2 methyl ester was also synthesized.