Concise Synthesis of Glycerophospholipids

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.