Synthesis of the antitumoral nucleoside capecitabine through a chemo-enzymatic approach

Abstract

Capecitabine is a 5′-deoxynucleoside endowed with antitumoral activity. We planned a new approach to its synthesis: a cross linked enzyme aggregate subtilisin (Alcalase CLEA)-catalyzed alcoholysis allowed the selective deprotection of primary acetyl ester of the N1-(2′,3′,5′-tri-O-acetyl-β-d-ribofuranosyl)-5-fluoro-N4-(n-pentyloxycarbonyl)cytosine affording the corresponding 5′-hydroxyderivative; the 5′-alcohol was transformed into the methyl group of capecitabine after a careful investigation about the best reducing agent and reaction conditions.