SYNTHESIS OF OPTICALLY-ACTIVE 1-ACYL-2-O-ALKYL-SN-GLYCERO-3-PHOSPHOCHOLINE VIA 1-O-BENZYL-SN-GLYCEROL 3-ARENESULFONATE

A stereocontrolled route to 1-palmitoyl-2-O-hexadecyl-sn-glycero-3-phosphocholine from (R)-glycidyl tosylate is described. This method gives very high enantioselectivity (93-96% enantiometric excess) and can be used to prepare 3-acyl-2-O-alkyl-sn-glycero-1-phosphocholines from (S)-glycidyl tosylate. The key step is the preparation of 1-O-benzyl-sn-glycerol 3-tosylate by the boron trifluoride etherate catalyzed regio- and stereo-specific opening of the epoxide ring with excess benzyl alcohol. The alkyl group is introduced using alkyl trifluoromethanesulfonate in the presence of excess 2,6-di-tert-butyl-4-methylpyridine. Debenzylation gives 2-O-alkyl-sn-glycerol 3-arenesulfonate, which is acylated and then converted into the phosphocholine. The use of chiral glycidyl derivatives as starting materials for the synthesis of glycerophospholipids is discussed.