Facile and regioselective enzymatic 5′-galactosylation of pyrimidine 2′-deoxynucleosides catalyzed by β-glycosidase from bovine liver

A regioselective enzymatic approach to 5′-O-galactosylated derivatives of pyrimidine 2′-deoxynucleosides was described. With o-nitrophenyl β-d-galactoside as glycosyl donor, galactosylation reactions of 2′-deoxynucleosides were mediated by a commercial β-galactosidase from bovine liver, affording 5′-O-galactosylated derivatives with the yields of 45–85% and 5′-regioselectivities of 92–100%. The study of enzyme substrate recognition revealed that the β-galactosidase performance showed a clear dependence on R-group present in the base moiety of 2′-deoxynucleoside. Besides, such desirable products were synthesized with satisfactory yields (41–68%) and moderate to high 5′-regioselectivities (87–100%) by using the crude enzyme extract.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of 5′-galactosylated derivatives of pyrimidine 2′-deoxynucleosides were synthesized using bovine liver β-galactosidase with satisfactory yields and good regioselectivities. ► There is a strong correlation between the structures of 2′-deoxynucleosides and the enzyme performance. ► The crude β-glycosidase extract is also a good catalyst for the synthesis of these galactosylated derivatives.