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The work described in this thesis focused on exploration of the versatile chemistry of boron to access functionalised bicyclic and acyclic boron-containing structures for use as enzyme inhibitors. Cyclic boronic acids/esters are emerging as promising scaffolds for broad-spectrum inhibition of β-lactamases, which are the most clinically relevant determinant of antimicrobial resistance to β-lactam antibiotics in Gram-negative organisms. The work included the development of novel stereoselective synthetic strategies, mechanistic studies, as well as method development for the bicyclic boronic acid pharmacophore. Development of novel methodology to access highly functionalised α-acylamido bicyclic boronate taniborbactam (TAN) is described in Chapter 2. Bicyclic boronates are very broad-spectrum β-lactamase inhibitors and have considerable clinical potential, having inhibitory activity against both serine- and metallo-β-lactamases (SBLs and MBLs, respectively). TAN was synthesised in eleven steps in 3% overall yield, which represents up to 750-fold yield improvement over previously reported syntheses of structurally related compounds. Subsequent biochemical and structural observations obtained through collaborations are described. An unexpected intramolecular cyclisation of the C-3 acylamido oxygen atom of TAN onto the boron of the bicyclic core was observed crystallographically in the complex of TAN with the subclass B1 MBL New Delhi metallo-β-lactamase-1 (NDM-1). The mechanistic proposal for the formation of this previously unobserved tricyclic inhibitor form and its biological significance are discussed. Building on this discovery, comparative analyses of binding modes of TAN and its analogues revealed a striking conservation in the conformations adopted by the fused bicyclic boronate core across SBLs and MBLs. Substantial variations in the acylamino side chain orientations were observed in the complex crystal structures. Studies on the synthesis and inhibitory properties of other fused 6,6-bicyclic boronate analogues with non-α-acylamido side chains are also described in Chapter 2. The synthetic results include an unexpected intramolecular Grignard reaction between an N-tert-butoxycarbonyl group and adjacent carboxylic ester giving rise to a novel borolactone structure. The SBL/MBL inhibition results suggest that there remains scope for side chain optimisation. Structure-based drug design and fragment-based drug design approaches were used to investigate the boronate pharmacophore in Chapters 3 and 4. Routes to bicyclic boronates and acyclic boronic acids were developed. The effects of ring size of the boronate core (6,6- versus 6,5-systems) and the presence of a carboxylate group were examined in the context of MBL inhibition in Chapter 3. Based on biochemical, structural and computational analyses, a pharmacophore fragment was selected for further optimisation studies, yielding potent MBL inhibitors comprising a benzoxaborole with a C-3 sulfonamide side chain (Chapter 4). Overall, the results described in this thesis enable the stereoselective synthesis of α-acylamido bicyclic boronates in improved yields and highlight the therapeutic potential of bicyclic boronates for β-lactamase inhibition. They also showcase the chameleon-like behaviour of organoboron compounds, including in their interactions with proteins.