Synthesis of novel 3′-azido-3′-deoxy-α-L-ribo configured nucleosides: A comparative study between chemical and chemo-enzymatic methodologies

Syntheses of novel 3′-azido-3′-deoxy-2′-O,4′-C-methylene-α-L-ribofuranosyl nucleosides have been carried out from 3′-azido-3′-deoxy-4′-C-hydroxymethyl-β-D-xylofuranosyl nucleosides following both chemical and chemo-enzymatic methodologies. The precursor nucleoside in turn was synthesized from a common glycosyl donor 4-C-acetoxymethyl-1,2,5-tri-O-acetyl-3-azido-3-deoxy-α,β-D-xylofuranose, which was obtained by the acetolysis of 4-C-acetoxymethyl-5-O-acetyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-D-xylofuranose in 96% yield. It has been observed that a chemo-enzymatic pathway for the synthesis of targeted nucleosides is much more efficient than a chemical pathway, leading to the improvement in yield for the synthesis of 3′-azido-3′-deoxy-α-L-ribofuranosyl thymine and uracil from 49 to 89% and 55 to 93%, respectively.