Practical and Divergent Synthesis of Carbocyclic Pyrazolo[3,4‐d]pyrimidine Nucleoside Analogues.

A concise set of 4‐substituted pyrazolo[3,4‐d]pyrimidine carboriboside analogues was synthesized in a divergent fashion via a central intermediate. An oxaziridine reagent allowed the synthesis of a crucial hydrazine glycon intermediate, which was transformed through a base‐build‐up strategy into the desired intermediate using a commercially available pyrimidine building block. Reaction with a variety of nucleophiles allowed late‐stage diversification. All analogues were evaluated for activity against a representative panel of Trypanosomatida. A methoxy‐substituted analogue displayed single‐digit micromolar activity against two subspecies of Trypanosoma brucei in cellular assays. [ABSTRACT FROM AUTHOR]