Synthesis of very short chain lysophosphatidyloligodeoxynucleotides

Very short chain 5?-O-lysophosphatidyloligonucleotides [5?-O-(1-0-palmitoyl-sn-glycero-3-phosphoryl)oligodeoxynucleotides, (5?-LyPOdNs)] were synthesized following a two-step chemoenzymatic synthesis. 5?-O-(in-Glycero-3-phosphoryl)oligodeoxynucleotides (5?-GPOdNs) were first prepared by simply using a phosphoramidite of [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (1) in a further coupling step after the solid-phase elongation of each desired oligodeoxynucleotide. Next, the regioselective palmitoylation at the C-1 hydroxyl of the glycerol moiety of 5?-GPOdNs was achieved by a lipase-catalyzed transacylation with trifluoroethyl palmitate in organic solvent. Despite of the molecular bulkiness of 5?-GPOdNs, 2-, 3-, and 4-mer 5?-LyPOdNs were prepared by this procedure. Although in very low yield, 5- and 6-mer 5?-LyPOdNs were also obtained by this way. © 2006 American Chemical Society.