Phosphatidylserine is a phospholipid found in cell membranes recognized as a calcium ion receptor in apoptosis and blood coagulation. Our project goal is to create phosphatidylserine lipid analogues (PLAs) to characterize calcium interaction between membranes and surface proteins. 1H and 31P NMR were used to follow a one-pot synthesis involving H-phosphonate chemistry and an acyl-chloride activator.  The starting alcohol, carbobenzyloxy-L-serine benzyl ester (CBZ-Ser-Bzl), was coupled with phosphonic acid using pivaloyl chloride followed by addition of cyclohexanol with additional pivaloyl chloride to form the desired H-phosphonate diester.  Multistep purification, using coevaporation, aqueous washes, and trituration yielded the desired product which was associated tightly with a molecule of unreacted CBZ-Ser-Bzl, possibly by some combination of hydrogen bonding and pi-pi stacking. Results show the one-pot synthesis was ineffective due to formation of undesired H-phosphonate diesters causing substantial purification difficulties.  The H-phosphonate monoester is being synthesized and purified for use in a two-step procedure.

Synthesis and purification of cyclohexylphosphoserine lipid analogs

245th National Meeting (2013)

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