Acid-Promoted Cyclization Reaction of the Guanine Base with 1,1,3,3-Tetramethoxypropane: A Method for the Preparation of M1 dG 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 (M1 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 M1 dG (6) and M1 G (9) Basic Protocol 3 Synthesis of tricyclic nucleotide (12).