B.S., University of Michigan, 1952; Ph.D., Columbia University, 1957; Postdoctoral Research Fellow, Harvard University, 1957 - 1959.
National Institutes of Health Special Fellow, Stanford University, 1965; Visiting Professor, University of Strasbourg, 1971; University of Grenoble; Editor, The Synthesis of Natural Products, 1994-1995.
Current Research Interests
My students and I are interested in the synthesis of biologically active natural products and in the development of new synthetic methods for total synthesis. In total synthesis, we are particularly interested in sesquiterpenes and diterpenes which either contain a quinone ring or can be derived from quinone precursors.
Quinones are widespread in nature and exhibit a variety of activities ranging from anti-inflammatory, to anticancer, antibiotic action. In addition, the quinone ring system through Diels-Alder cycloaddition chemistry readily lends itself to the construction of highly functionalized bicyclic systems.
Among the natural products of interest in our laboratory are the sesquiterpene quinones exemplified by avarone, aernarone, and the marine alkaloid discorhabin-C. The structures of the two sesquiterpenes, as well as the many diterepenes of the clerodane class, also lend themselves to synthesis using quinones as precursors for the decalin ring system of the natural products. For example, we have recently published syntheses of ajugarin-IV and annonene in which a quinone Diels-Alder reaction was employed.
One of the most efficient methods for constructing polyclic molecules is the cyclization of acycyclic polyenes and polyene epoxides. These reactions are not enantioselective, however. For example, the cyclization of 1, affords 2, but the tricyclic product is racemic. We are now investigating methods for carrying out such a cyclization in the presence of a chiral Lewis acid.
We are also synthesizing potential chiral brominating agents. These are intended to convert polyenes into one enatiomer of the corresponding bromohydrin. Further transformation will yield a chiral epoxide which may then be submitted to cyclizing conditions.
We are also interested in exploring the utility of the base-catalyzed opening of cyclopropyl ketones as a method for remote alkylation. For example, when keto-alcohol 3 is treated with base it undergoes a cleavage reaction followed by a recyclization to form tricyclic ether 4. Treatment of 4, however, with a Lewis acid and acetic anhydride provides enone 5. Thus a methyl group has been introduced into the g-position of an a,b-ketone. Currently we are extending this methodology to a variety of other substrates.
Recent Publications
Goldsmith, D.J.; Robinson, T.P.; Furness, M.S. and Bowen, J.P. "An Efficient Synthesis of 2-Aryl and 2-Alkenyl-3-Alboxycyclohexenones by a Modified Stille Reaction." Tetrahedron Lett., 1999, 40, 459. |
