Functionalizing Nucleobases With Boronic Acids and Boronic Acid Esters: Thymine Derivatives and Their Dioxazaborocane Chemistry

Boronic acid-substituted thymine derivatives are well established and exhibit a range of biological activities. In contrast, the corresponding boronic acid esters and dioxazaborocane analogs remain largely unexplored. Herein, we report the synthesis and structural characterization of thymine derivatives bearing boronic acid, boronic acid ester, and dioxazaborocane motifs using single crystal X-ray diffraction and NMR spectroscopic and mass spectrometric analyses, thereby providing synthetic access to, and structural characterization of, a broader range of boron-functionalized thymine derivatives. Moreover, a synthesis for a dioxazaborocane-containing thymine derivative featuring a CC double bond for further functionalization (e.g., with a second dioxazaborocane unit) is presented together with its solid-state structure. Additional dioxazaborocane derivatives without a nucleobase scaffold serving as model compounds for methodology development demonstrated selective transesterification of a pinacol boronic acid ester to a second dioxazaborocane unit . Comparative analysis indicates that the thymine substituent drives the main structural differences by enabling intermolecular hydrogen bonding. These findings expand the scope of functionalized nucleobases and provide synthetic access as well as the first comprehensive structural insights into dioxazaborocane-containing thymine derivatives.