Concise Synthesis of Glycerophospholipids

Abstract

Glycerophospholipids are major components of cellular membranes and provide important signaling molecules. Besides shaping membrane properties, some bind to specific receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening of a phosphate triester epoxide with carboxylic acids catalyzed by Jacobsen’s Co(salen) complex. We show that this method can be applied to a variety of commercially available fatty acids, photoswitchable fatty acids, and other carboxylic acids to provide the corresponding glycerophosphate derivatives.