Biocatalytic route to C-3'-azido/-hydroxy-C-4'-spiro-oxetanoribonucleosides

The lipase, Novozyme(®)-435, exclusively deacetylates the 5-O-acetyl over 4-C-acetyloxymethyl group of almost identical reactivity in 5-O-acetyl-4-C-acetyloxymethyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-D-ribofuranose that led to the development of first and efficient synthesis of 3'-azido-/3'-amino-C-4'-spiro-oxetanoribonucleosides T, U, C and A in 20-24% overall yields. The X-ray study on the compound obtained by tosylation of lipase-mediated monodeacetylated product unambiguously confirmed the point of diastereoselective monodeacetylation on diacetoxy-azido-ribofuranose derivative. The capability of Novozyme(®)-435 for selective deacylation of 5-O-acetyl group in 5-O-acetyl-4-C-acetyloxymethyl-3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranose recently discovered by us has been successfully used for the synthesis of C-4'-spiro-oxetanoribonucleosides A and C in good yields. These results clearly indicate that the broader substrate specificity and highly selective capability of Novozyme(®)-435 for carrying out acetylation/deacetylation reactions can be utilized for the development of environment friendly selective methodologies in organic synthesis.