First total synthesis of the anti-inflammatory lipid mediator Resolvin D6

The first total synthesis of Resolvin D6, an endogenous lipid mediator of resolution of inflammation derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C4 and C17 were generated via an asymmetric Noyori transfer hydrogenation and a Sharpless catalytic asymmetric epoxidation, respectively. A mild copper catalyzed coupling of cis-1,4-dibromo-2-butene with TMS-acetylene generated the C7-C14 fragment. Pd0/CuI Sonogashira couplings and Zn(Cu/Ag) reduction completed the synthesis of Resolvin D6.