The enzymatic oxygenation of docosahexaenoic acid (DHA) by macrophages was shown to generate several new series of DHA-derived lipid mediators, which promote the resolution of inflammation and tissue regeneration. These include Maresin 1(MaR1), Maresin 2 (MaR2), the precursor epoxide 13S,14S,-epoxy Maresin (13,14-eMaR), and the recently identified maresin conjugate tissue regenerative series (MCTR1, MCTR2, and MCTR3). These enzymatically-derived macrophage-derived specialized pro-resolving lipid mediators (SPM) were shown to have stereochemically defined structures. Each of these lipid metabolites features a distinct positioning of carbon-carbon double bonds with specific Z/E geometry, and contains substituted heteroatoms with specific R/S configurations. In order to elucidate the complete stereochemistry of thesenovel SPM, we have developed stereocontrolled total synthesis approaches that produced stereochemically pure materials, as well as selected stereoisomers. Herein, we detailed our recent efforts involving several members of this class of compounds, including the stereocontrolled total synthesis of MaR2, and the members of the maresin conjugate tissue regenerative series (MCTR1, MCTR2, and MCTR3). These synthetic materials are helpful to unambiguously establish the native stereochemistry of these lipid mediators, and to investigate their novel biological actions, which include the promotion of the resolution of inflammation and tissue regeneration.

Stereocontrolled total synthesis of macrophage-derived specialized pro-resolving lipid mediators

251st National Meeting (2016)

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