CHEMOENZYMATIC SYNTHESIS OF LYSOPHOSPHATIDYLNUCLEOSIDES

5'-O-Lysophosphatidylnucleosides '-O-(1-O-acyl-sn-glycero-3-phosphoryl )nucleosides] were obtained by a two-step chemoenzymatic synthesis. 5' -O-(sn-Glycero-3-phosphoryl)nucleosides (5'-GPNs) were first prepared from a phosphoramidite of 1,2-O-isopropylidene-sn-glycerol and appropr iately protected nucleosides, applying the phosphoramidite methodology on the solid phase or in solution. In a following step, the regiosele ctive acylation at the C-l hydroxyl of the glycerol moiety of 5'-GPNs was achieved by a lipase-catalyzed transacylation with activated fatty acid esters in organic solvent. Some deoxyribo- and ribonucleosides, as well, were converted into the corresponding lysophosphatidyl deriva tives utilizing either saturated or unsaturated fatty acid esters with different length alkyl chains. The synthesis was also applied to the preparation of O-(1-O-palmitoyl-sn-glycero-3-phosphoryl) conjugates of Acyclovir and AZT, of potential pharmacological interest.