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

GRAPHICAL ABSTRACT

ABSTRACT

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.

KEYWORDS:

• diastereoselective
• biocatalysis
• novozyme®-435
• 3′-azido-3′-deoxy-α-L-ribofuranosyl nucleosides

Acknowledgements

We are grateful to the University of Delhi for providing financial support under DU-DST Purse Grant and under scheme to strengthen research and development. We are also thankful to CIF-USIC University of Delhi, Delhi, for providing crystallographic data and NMR spectral recording facility. N. R. and M. K. thank CSIR for the award of Senior Research Fellowships and P. S. thanks Department of Health Research- HRD.