Acid-Promoted Cyclization Reaction of the Guanine Base with 1,1,3,3-Tetramethoxypropane: A Method for the Preparation of M dG and its Derivatives.

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 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 dG (6) and M G (9) Basic Protocol 3: Synthesis of tricyclic nucleotide (12).