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

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.

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

“…Further, Zhang et al [ 23 ] synthesized the tricyclic azido-isonucleoside analogue 5 and Imanishi et al [ 24 ] synthesized the azido-nucleoside 6 with a conformationally restricted sugar moiety. Recently, we have developed a greener and efficient chemoenzymatic synthetic methodology for the synthesis of conformationally restricted bicyclic azido-nucleosides 6 [ 25 ] and 7 [ 26 ], and bicyclic homonucleosides 8 [ 27 ]. Herein, we report an efficient chemo-enzymatic and chemical route to synthesize two novel conformationally restricted azido-homoarabino nucleosides 9a , b in excellent overall yields ( Figure 1 ).…”