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

Abstract

3-(2-Deoxy-β-d-erythropentofuranosyl)pyrimido[1,2-a]purin-10(3H)-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.