Chemo-enzymatic synthesis of 3′-O,4′-C-methylene-linked α-l-arabinonucleosides

Abstract

Lipozyme® TL IM catalyzed the diastereoselective acetylation of C-4′-hydroxymethyl over the other three hydroxyl groups of C-4′-hydroxymethyl-β-D-xylofuranosylnucleosides using vinyl acetate as acetyl donor to afford the corresponding C-4′-acetoxymethylnucleosides in 88 to 95% yields. The developed biocatalytic methodology has been successfully used for the efficient and environmentally friendly synthesis of 3′-O,4′-C-methylene-linked α-L-arabinofuranosylnucleosides from enzymatically monoacetylated nucleosides in 63 to 79% overall yields. The screening of vinyl esters of different alkyl chain lengths, i.e. vinyl acetate, vinyl propanoate and vinyl butanoate as acylating agent for biocatalytic diastereoselective acylation of the C-4′-hydroxymethyl group of tetrahydroxy-β-D-xylofuranosylthymine revealed that the rate of butanoylation and propanoylation is 2.0 and 1.5 times faster than that of acetylation, respectively.