Stereocontrolled synthesis and investigation of the biosynthetic transformations of 16(S),17(S)-epoxy-PD.

PD1 is a specialized pro-resolving lipid mediator that displays potent anti-inflammatory properties and pro-resolving bioactivities. Such naturally occurring compounds are of current interest in biomolecular chemistry and drug discovery. To investigate the involvement of an epoxide intermediate in the biosynthesis of PD1 from n-3 docosapentaenoic acid, the epoxy acid 16(S),17(S)-epoxy-PD, herein named ePD, was prepared by stereoselective total synthesis. The synthetic material of ePD allowed investigations of its role in the biosynthesis of PD1. The obtained results establish that the biosynthesis of PD1 in neutrophils occurs with ePD as the intermediate, and that 15-LOX produces ePD from n-3 docosapentaenoic acid. Furthermore, support for the involvement of a hydrolytic enzyme in the biosynthetic conversion of ePD to PD1 was found. In addition, ePD was found to regulate the formation of the potent neutrophil chemoattractant LTB with equal potencies to that obtained with PD1.