Boronic acid transition state inhibitors (BATSIs) represent one of the most promising class of β-lactamase inhibitors. Here we describe a new class of BATSIs, namely 1-amido-2-triazolylethaneboronic acids, which were synthesized combining the asymmetric homologation of boronates with Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) for the stereoselective insertion of the amido group and the regioselective formation of the 1,4-disubstituted triazole, respectively. This synthetic pathway, which avoids intermediate purifications, proved to be flexible and efficient, affording in good yields a panel of fourteen BATSIs bearing three different R1 amide side chains (acetamido, benzylamido and 2-thienylacetamido) and several R substituents on the triazole. This small library was tested against two clinically relevant class C β-lactamases from Enterobacter spp. and Pseudomonas aeruginosa. The Ki value of the best compound (13a) was as low as 4 nM with significant reduction of bacterial resistance to the combination of cefotaxime/13a.

New alkenylboronic esters were synthesised from halo-substituted alkenylboronic esters through cross-coupling reactions. Upon Johnson rearrangement, enantiomerically pure allylboronates bearing a stereogenic centre in the position α to the boron moiety were obtained in moderate yield (53 %; 29 % over six steps from the protected propargylic alcohols). The

Diastereomerically pure allylboronates bearing the readily available tartrate derivative were obtained via sigmatropic rearrangement. Allyl additions were performed, and the influence of γ-disubstituted allylboronates was studied. Highly γ-substituted boronic esters were found to lead to the corresponding enantiomerically enriched homoallyl alcohols with exclusively E configuration; their synthesis and the mechanism of the reaction is proposed here.