Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

Abstract

Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility.

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…338 N435 catalyzed the selective production of 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-riboand xylofuranose which can be utilized for the convergent synthesis of two different types of bicyclic nucleosides. 339 Moreover, N435 has been utilized to produce glucosyl monoester surfactants using N-fatty acyl amino acid and D-glucose. 340 N435 has been used to produce 2′,3′,5′-tri-O-ace-tyl-4′-C-p-toluenesulfonyloxymethyl-β-D-xylofuranosylthymine and 2′,3′,5′-tri-O-acetyl-4′-C-p-toluenesulfonyloxymethyl-β-Dxylofuranosyluracil was used to produce C-4′-spiro-oxetano-α-Lribonucleosides.…”