Diversification of 3′-Amino Nucleosides via Enzymatic Transglycosylation

Graphical Diversification of commercially available 3’-amino-3’-deoxythymidine via nucleoside phosphorylase Ec PPNP- and/or nucleoside 2’-deoxyribosyltransferase Ll NDT-catalyzed transglycosylation has been demonstrated as a generally applicable, straightforward means to access a variety of valuable 3’-amino containing nucleosides in good yields. The synthetic utility was further showcased by the successful synthesis of 3’-amino-2’,3’-dideoxy-5-bromouridine in 29% isolated yield at a preparative scale. 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 Ec PPNP- and/or nucleoside 2′-deoxyribosyltransferase Ll NDT-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 Ec PPNP for the first time, expands the substrate scope of Ll NDT, and provides an efficient, direct access to various 3′-amino nucleosides of high value.