Diversification of 3′-Amino Nucleosides via Enzymatic Transglycosylation

Abstract

A systematic study on the enzymatic transglycosylation of 3′-amino nucleosides has been reported. Using the commercially available 3′-amino-3′-deoxythymidine as the sugar donor, 13 pyrimidine and purine nucleobases were shown as the viable sugar acceptors in the nucleoside phosphorylase EcPPNP- and/or nucleoside 2′-deoxyribosyltransferase LlNDT-catalyzed reactions, furnishing the corresponding 3′-amino containing nucleosides in 23%–73% NMR yields at an analytical scale. The synthetic utility of this diversification approach was further showcased by the successful synthesis of 3′-amino-2′,3′-dideoxy-5-bromouridine in 29% isolated yield at a preparative scale. The current work demonstrates the transglycosylation activity of EcPPNP for the first time, expands the substrate scope of LlNDT, and provides an efficient, direct access to various 3′-amino nucleosides of high value.