Electrophilic Deboronations in Synthesis

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Jeremy May of the University of Houston is studying the development of new heavy metal-free chemical reactions to synthesize complicated molecular structures needed for advanced materials, pharmaceutical agents, and other carbon-based compounds. Most pharmaceutical remedies rely on carbon-based molecules, where greater complexity and three-dimensionality improve the pharmacological profile and selectivity for the disease target. However, desirable molecules with great complexity or with many oxygen, nitrogen, or sulfur atoms are challenging to synthesize. This difficulty is due to side reactions and barriers to reactivity from the density of bonds in the construction. This project leverages a novel catalytic phenomenon to reduce those barriers while making densely functionalized molecules of relevance to the study and treatment of disease. The May group is also synthesizing a library of molecules having a special molecular motif that confers strong and beneficial biological effects in naturally occurring molecules, providing new lead compounds for disease treatment. These activities are complemented by educational days with local charter schools and high schools to increase enthusiasm and literacy in science. Enantioselective and diastereoselective methods for the installation of quaternary carbon centers are a long standing challenge in synthetic chemistry. Prof. May and his research group are investigating the use of the ouroboros transition state's precise regioselectivity and enhanced activation to facilitate enantioselective reactions in traditionally unreactive systems. This generality of this strategy is being explored and used to design new applications. The mild reaction conditions required of electrophilic deboronations are also being used to study a general approach for the synthesis of natural products with 3-indole propylene glycol motifs and developed as a method for the functionalization and alteration of molecules with known bioactivity. These research activities are further providing a rigorous training environments for graduate and undergraduate students in synthetic organic chemistry and generating libraries of new molecules that are tested at screening centers to identify new lead compounds for development. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.