Facile Synthesis of 5′-Deoxy- and 2′,5′-Dideoxy-6-thiopurine Nucleosides by Nucleoside Phosphorylases.

Abstract 5′-Deoxy-6-thioguanosine, 2′,5′-dideoxy-6-thioguanosine, 5′-deoxy-6-mercaptopurine riboside and 2′,5′-dideoxy-6-mercaptopurine riboside were synthesized enzymatically from thiopurine bases and corresponding ribosyl donors using nucleoside phosphorylase. This is the first report of trans-5′-deoxyribosylation to thiopurine bases by nucleoside phosphorylase. 5′-Deoxy-6-thioguanosine selectively blocked the growth of v-ras-transformed human bronchial epithelial cells. In addition, the in vitro antitumor cytotoxicity data for 5′-deoxy- and 2′,5′-dideoxy-6-thiopurine nucleosides were comparable to those for the corresponding thiopurine bases.