Enantiopure β-isocyano-boronic esters: synthesis and exploitation in isocyanide-based multicomponent reactions

Abstract

Various boron-containing isocyanides have been efficiently synthesized from the corresponding enantiopure β-substituted β-amino boronic acid pinacol esters, without need for protecting group interconversion, through a two-step, purification-free procedure. They were employed in a variety of isocyanide-based multicomponent reactions, proving to be reliable components for all of them and allowing the efficient synthesis of unprecedented, boron-containing peptidomimetics and heteroatom-rich small molecules, including biologically relevant cyclic boronates. Jointing together the β-amido boronic acid moiety, deriving from the isocyanide component, with prominent pharmacophoric rings emerging from the multicomponent process, a successful application of the molecular hybridization concept could be realized. Graphical abstract

Computational Design, Synthesis, and Biophysical Evaluation of β-Amido Boronic Acids as SARS-CoV-2 Mpro Inhibitors

“…Based on the computational studies, the β-amido boronic acids reported in Table 1 were synthesized. Relying on our previous experience [18,19], the Ugi multi-component reaction (Ugi-4CR) was chosen as the key step for the synthesis of boron-enriched peptidomimetics. Starting from enantiopure β-amino boronic acid hydrochloride 1 and formaldehyde (fixed amino and carbonyl components, respectively), a series of selected acids and isocyanides were employed in the reaction.…”