Synthesis of Nucleoside and Nucleotide Analogues by Cyclization of the Guanine Base with 1,1,3,3-Tetramethoxypropane.

3-(2-Deoxy-β-d-erythropentofuranosyl)pyrimido[1,2-<i>a</i>]purin-10(3<i>H</i>)-one (M₁dG) is an endogenous DNA adduct in bacterial and mammalian cells that could be explored as a biomarker for oxidative stress. Nonetheless, the lack of an efficient methodology for the preparation of M₁dG hampers the deep investigation of its biosynthesis and biorelevant processes. In this project, we aimed to address this issue by developing a highly efficient method to synthesize M₁dG and its analogues. This method has wide functional group tolerance, as various guanine-based nucleosides and nucleotides are suitable for the reaction. Furthermore, large-scale and derivatization reactions were carried out to showcase the possibility for biochemists to study DNA damage and repair processes in the future.