Rapid and reliable access to synthetically-derived chemical structures plays an essential role in many aspects of biomedical research. The underlying objective of the parent award is to provide fundamentally new strategies for highly selective bond formations that will enable more rapid and efficient access to biologically active compounds of potential therapeutic value. Using small molecule transition metal catalysts, the regioselective derivatization of simple structural subunits such as alkenes and alkynes will be addressed. Through careful mechanistic analysis, new insights will be provided to guide general strategies toward this objective in a broad range of contexts. Using engineered biological catalysts, strategies will be developed to enable regioselective oxidations of C-H bonds in complex substrates, using a novel substrate engineering approach that directs cytochrome P450-mediated oxidations towards a desired C-H bond embedded within a complex molecular framework. The goals of this research program will provide highly effective strategies for impacting and enhancing the biological properties of complex structures. The improved entries to biomedically important structures made possible by this research will enable their biological function and therapeutic potential to be more efficiently studied. This supplement application requests funds for purchase of a Gas Chromatography ? Mass Spectrometry (GCMS) instrument. This instrument will greatly increase both the accuracy and the speed of analyses conducted on the projects described above. These improvements will enable new discoveries and will increase productivity and efficiency of our group personnel funded on the parent award.
The goal of this research effort is to develop versatile new methods for the preparation of compounds of biomedical significance. Through a multidisciplinary approach, improvements in the speed, efficiency, selectivity, and cost of introducing structural subunits that impact the biological properties and function of complex structures will be developed. A new Gas Chromatography ? Mass Spectrometry instrument is requested that will advance the goals of this effort and enable new discoveries.
| Shimkin, Kirk W; Montgomery, John (2018) Synthesis of Tetrasubstituted Alkenes by Tandem Metallacycle Formation/Cross-Electrophile Coupling. J Am Chem Soc 140:7074-7078 |
| Nett, Alex J; Cañellas, Santiago; Higuchi, Yuki et al. (2018) Stable, Well-Defined Nickel(0) Catalysts for Catalytic C-C and C-N Bond Formation. ACS Catal 8:6606-6611 |
| Wang, Hengbin; Lu, Gang; Sormunen, Grant J et al. (2017) NHC Ligands Tailored for Simultaneous Regio- and Enantiocontrol in Nickel-Catalyzed Reductive Couplings. J Am Chem Soc 139:9317-9324 |
| Gilbert, Michael M; DeMars 2nd, Matthew D; Yang, Song et al. (2017) Synthesis of Diverse 11- and 12-Membered Macrolactones from a Common Linear Substrate Using a Single Biocatalyst. ACS Cent Sci 3:1304-1310 |
| Kerchner, Hilary A; Montgomery, John (2016) Synthesis of Secondary and Tertiary Alkylboranes via Formal Hydroboration of Terminal and 1,1-Disubstituted Alkenes. Org Lett 18:5760-5763 |
