First total synthesis of the anti-inflammatory and pro-resolving lipid mediator 16(R),17(S)-diHDHA

Abstract

The first total synthesis of the anti-inflammatory and pro-resolving lipid mediator 16(R),17(S)-diHDHA, derived from docosahexaenoic acid (DHA), and its 16-epimer have been achieved. Two synthetic approaches are described for the synthesis of 16(R),17(S)-diHDHA. The first strategy started from DHA and used an enzymatic reaction, a vanadium catalyzed allylic epoxidation and a base-promoted epoxide isomerization. The second approach utilized a chiral pool strategy starting from 2-deoxy-d-ribose to establish the chiral centers; Wittig reactions, mild acetonide cleavage and ester hydrolysis were the key steps in the synthesis.