The research outlined within this proposal will establish new knowledge in the following three areas: 1) Access to novel borazine structures will be explored, and the usefulness of these isosteres of all-carbon systems for predictable, highly selective, polyfunctionalization of valuable core structures will be demonstrated. 2) Photoredox/Ni dual catalysis for cross-coupling of sp3- hybridized centers was pioneered in our group. These are transformative processes that have, in an elegant and practical manner, provided the necessary tools to open vast new areas of 3D chemical space through late-stage cross-coupling in highly functionalized substructures. Continued innovation will focus on three subtopics: further expansion of the photoredox/Ni dual catalysis, application of photoredox for application to novel radical transformations, and the invention of novel radical/polar crossover transformations based on photoredox chemistry. 3) As a result of progress made within the scope of current grants, an amazing new opportunity to expand our chemistry has arisen that will provide transformational new tools for drug discovery. Methods developed in the group are being applied to DNA Encoded Library (DEL) synthesis, a technology that possesses the capability to sample easily four to five orders of magnitude more chemical space, less expensively, than any other available high-throughput, small molecule screening methods. It is widely acknowledged that the major hurdle to full implementation of DEL technology is the development of robust, versatile, DNA-compatible chemistry, which is currently exceedingly limited in scope and application. The chemistry outlined in this proposal addresses this critical gap, and thus has the capability to revolutionize the drug discovery process.
As an enabling science, chemistry has the unique ability to transcend disease areas, influencing and even revolutionizing the treatment of all manner of human afflictions. The research outlined in this proposal will facilitate drug discovery through the development of novel synthetic methods and the creation of unprecedented molecular platforms. These methods will benefit scientists in a variety of academic and industrial settings owing to their mildness, efficiency, low cost, versatility and practicality.
