Expanding the Chemical and Functional Space with Boron-Nitrogen Heterocycles

Project Summary/Abstract The generation of chemical space and its translation into new functions is one of the main goals of synthetic chemistry. The BN/CC isosterism (i.e., replacement of a carbon-carbon bond with a boron-nitrogen bond) has emerged as a viable strategy to increase the chemical space of compounds relevant to biomedical research. We seek to develop enabling tools that are provided by the new expanded chemical space through BN/CC isosterism of arenes: a) In the field of synthetic organic chemistry, we aim to 1) explore novel reactivity and selectivity that are unattainable by using “conventional” non-boron-containing organic compounds, and 2) discover and exploit new mechanistic principles for synthesis/catalysis, both as a consequence of the unique electronic structure created by BN heterocycles. When addressed, synthetic chemists will enjoy · new ligands that support metal-catalyzed reactions with distinct reactivity/selectivity, and · a versatile 4C+1N+1B synthon for synthesis. b) In the field of chemical biology, we aim to utilize BN-indole and its corresponding amino acid BN- tryptophan to 1) create novel BN-alloproteins in both bacterial and mammalian cells, 2) develop a novel bioconjugation platform that is rapid, catalyst-free, chemoselective, and orthogonal to existing bioconjugation methods, 3) develop a novel isosteric intrinsic fluorophore for characterizing protein interactions. Completion of the proposed aims will yield new fundamental knowledge related to boron in the context of synthetic organic and biological chemistry. It will generate new synthetic methods and research tools for the investigation of biological processes and inspire the design and development of new boron-containing molecules for biomedical applications.