Phospholipid Synthesis Based on New Sequential Phosphate and Carboxylate Ester Bond Formation Steps

Article abstract of DOI:10.1021/jo00174a012

A total synthesis of racemic phosphatidylcholine is based on two novel but straightforward reaction sequences.The phosphate diester portion is constructed by successive displacement of the chlorines on methyl dichlorophosphate by allyl alcohol and dimethylethanolamine.The resulting triester isomerizes smoothly to allyl choline phosphate.The double bond is then converted to the bromohydrin to allow the sequential introduction of the two acyl ester linkages.Esterification of the hydroxyl with palmitoyl chloride produces 2-bromo-2-deoxylysophosphatidylcholine as the only isomer.The bromide is displaced in the final step upon treatment with the carboxylate form of an anion-exchange resin.The distinctive 31P-13C coupling patterns in the 13C resonances of the glycerol backbone allow the regiochemistry of the various steps to be conveniently monitored.Also, employment of palmitic-1-13C acid in the final step indicated a 70percent rearrangement accompanied formation of the mixed acid phosphatidylcholine.