Chemoenzymatic approach to the synthesis of the antiviral agents penciclovir and famciclovir in isotopically chiral [13C] labelled form

Abstract

The antiviral agents penciclovir and famciclovir have been synthesised in isotopically chiral [¹³C] form. The synthesis of (+)-methyl 4-benzyloxy-2-(hydroxymethyl)butanoate 12a by use of enzymatic hydrolysis catalysed by the lipase from Candida cylindracea is described as is the confirmation of the stereochemistry of this intermediate as R by convergent synthetic routes. The butanoate 12a produced by the enzymic reaction was converted into the (–)-α-hydroxymethyl-γ-butyrolactone which was compared with the (S)-(+)-α-hydroxymethyl-γ-butyrolactone synthesised by an alternative, stereodefined route. The products of the enzymic reaction were used as intermediates in the synthesis of the final products.