First total syntheses of the pro-resolving lipid mediators 7(S),13(R),20(S)-Resolvin T1 and 7(S),13(R)-Resolvin T4

Abstract

The first total syntheses of the pro-resolving lipid mediators 7(S),13(R),20(S)-Resolvin T1 [7(S),13(R),20(S)-RvT1] and 7(S),13(R)-Resolvin T4 [7(S),13(R)-RvT4], derived from n-3 docosapentaenoic acid (n-3 DPA), are described. 7(S),13(R),20(S)-RvT1 was prepared from 7(S),13(R)-RvT4 via an enzymatic lipoxidase reaction. 7(S),13(R)-RvT4 was obtained by total synthesis where the chiral centers at C7 and C13 where introduced by a Noyori transfer hydrogenation and a chiral pool strategy respectively. Wittig reactions, Sonogashira coupling and Boland Zn(Cu/Ag) reduction were the key steps in the synthesis.