- B. S. in chemistry, Marietta College, Marietta OH, 1975
- Ph.D. in organic chemistry, University of Wisconsin, Madison, WI, 1981
- Development of new tandem reaction methodology for the synthesis of cyclic compounds
- Synthesis of heterocyclic compounds
- Synthesis of new medicinal agents
- Study of organic reaction mechanisms
Much of our research has involved the exploration of tandem reaction methodology for the efficient preparation of heterocycles as potential drug compounds. Tandem reactions have gained considerable recognition in organic synthesis over the past 25 years. These processes link together several chemical transformations in a single reaction vessel, thus minimizing the number of laboratory operations needed and the amount of chemical waste generated during a synthesis. In a typical tandem process, an initial transformation generates an intermediate that can react sequentially with one or more functional groups present in the same molecule. Since the steps that occur after the initiating reaction are usually intramolecular, many of the problems associated with steric hindrance and chemoselectivity are minimized. Some examples of this synthetic strategy from our work include a reduction-reductive amination, a Michael-SNAr reaction, an SNAr-Michael reaction, a reduction-cycloaromatization-Friedel-Crafts reaction, an addition-elimination-SNAr reaction and an imine addition-SNAr reaction. We have also reported new conditions for the preparation of mono- and disubstituted 2,3-dihydro-4(1H)-quinazolinones from 2-nitro- and 2-amino-benzamide.
More recently, much of our effort has been directed towards the development of two new medicinal agents. The first is a benzothiopyran-based anticancer drug currently entering phase 1 trials. The second is a family of 2,4-diaminopyrimidine-based antibiotics, which are active against Bacillus anthracis and Staphalococcus aureus. Work is focused on generating more active derivatives of these agents as well as elucidating their mechanisms of action.