Acid‐Promoted Cyclization Reaction of the Guanine Base with 1,1,3,3‐Tetramethoxypropane: A Method for the Preparation of M1dG and its Derivatives

Abstract Despite the importance of nucleosides and nucleotides for drug discovery, only a few practical methods to prepare tricyclic nucleosides have been reported. Here, we describe a synthetic strategy for late‐stage functionalization of nucleosides and nucleotides via chemo‐ and site‐selective acid‐promoted intermolecular cyclization. The nucleoside analogs with an additional ring were obtained in moderate‐to‐high yields, including some antiviral drugs (acyclovir, ganciclovir, and penciclovir) derivatives, endogenous fused ring nucleoside (M 1 dG) and its derivatives, and nucleotide derivatives. © 2023 Wiley Periodicals LLC. Basic Protocol 1 : Synthesis of tricyclic acyclovir analogs ( 3a‐3c ) Basic Protocol 2 : Synthesis of tricyclic nucleosides M 1 dG ( 6 ) and M 1 G ( 9 ) Basic Protocol 3 : Synthesis of tricyclic nucleotide ( 12 )