Synthesis, reactivity and biological activity of N(4)-boronated derivatives of 2′-deoxycytidine

By seeking new stable boron-containing nucleoside derivatives, potential BNCT boron delivery agents, a novel synthetic approach was tested, aimed at a boron attachment via a single bond to an aliphatic carbon of sp3 hybridization. The latter allowed successful modification of deoxycytidine in the reaction with 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of the deoxynucleoside amino group. For new compounds, detailed NMR, LDI HRMS (Laser Desorption/Ionization High-Resolution Mass Spectrometry) analyses along with in vivo phosphorylation studies, toxicity assays and DFT modelling are presented.

By seeking new stable boron-containing nucleoside derivatives, potential BNCT boron delivery agents, a novel synthetic approach was tested. The successful modification of deoxycytidine gave several unique compounds of rarely found properties. For new compounds, detailed NMR, LDI HRMS analyses along with in vivo phosphorylation studies, toxicity assays and DFT modelling are presented.Figure optionsDownload as PowerPoint slide