First total synthesis of the pro-resolving lipid mediator 7(S),12(R),13(S)-Resolvin T2 and its 13(R)-epimer

Abstract

The first total synthesis of the pro-resolving lipid mediator 7(S),12(R),13(S)-Resolvin T2 [7(S),12(R),13(S)-RvT2] and its 13(R)-epimer, derived from n-3 docosapentaenoic acid (n-3 DPA), are described. 7(S),12(R),13(S)-RvT2 and its 13(R)-epimer were obtained by total synthesis using a chiral pool strategy to introduce the chiral centers. C7 was generated from S-(−)-1,2,4-butanetriol in both molecules and the C12 and C13 centers were generated from L-(+)-ribose and D-(−)-arabinose respectively. Cis and trans-selective Wittig reactions, selective deprotections, and Dess-Martin periodinane oxidation were the key steps in the syntheses.