LAUSR

6‐Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9‐(6‐Deoxy‐β‐D‐allofuranosyl)‐6‐methylpurine [methyl(allo)‐MePR, 18] and 9‐(6‐deoxy‐α‐L‐talofuranosyl)‐6‐methylpurine [methyl(talo)‐MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)‐MePR] and [methyl(talo)‐MePR] are described. The glycosyl donors, 1,2‐di‐O‐acetyl‐3,5‐di‐O‐benzyl‐α‐D‐allofuranose (12) and 1‐O‐acetyl‐3‐O‐benzyl‐2,5‐di‐O‐benzoyl‐α‐L‐talofuranose (16) were prepared from 1,2:5,6‐di‐O‐isopropylidene‐α‐D‐glucofuranose (4) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6‐methylpurine (3), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc.