Recent studies involving the role of lipid mediators during the inflammatory response, led to the identification of several new series of DHA-derived lipid metabolites, which promote the resolution of inflammation and accelerate tissue regeneration. These specialized pro-resolving mediators (SPMs) include the recently reported protectin-sulfido conjugate tissue regenerative series (PCTR1, PCTR2, and PCTR3). These novel SPMs are produced from the postulated 16S, 17S-epoxide precursor that leads to the biosynthesis of protectin D1/neuroprotectin D1 (PD1/NPD1). Opening of the protectin epoxide via a glutathione sulfur transferase enzymatic pathway leads to the formation of these PCTRs, which were shown to actively promote the resolution of acute inflammation and to accelerate tissue regeneration. Structurally, each of these SPMs is characterized by distinct docosahexaenoate backbone and sulfido-conjugated triene containing specific Z/E geometry and defined stereocenters. In order to validate the complete stereochemistry of these novel molecules and to further investigate their biological actions, we have developed stereocontrolled total synthesis approaches that produced stereochemically pure materials. Herein, we detailed our efforts involving the stereocontrolled total synthesis of the protectin 16S, 17S-epoxide precursor, as well as the PCTR series of SPMs. These synthetic materials are useful for unambiguously affirming the stereochemistry of these lipid mediators, and for the detailed investigation of their biological actions.

Stereocontrolled total synthesis of the DHA-derived protectin-related epoxide and sulfido-conjugates

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.