 Professor B.S. 1973, University of Wisconsin - Eau Claire Ph.D. 1978, University of Pittsburgh Room: 8132aPhone: 608-262-4941 Email: burke@chem.wisc.edu Position: Professor Selected Publications
| Research DescriptionOur research encompasses a broad range of synthetic and bioorganic projects. Natural products total synthesis and synthetic methods development continue to be areas of pursuit for us. Increasingly, we have become involved in the design, construction and study of novel, unnatural molecules to function as artificial receptors or conduits for molecular and ionic substrates. Molecules that exhibit important biological activity, challenging structural features, and low natural abundance are attractive synthetic targets. Discovery, development and application of new reactivities, strategies and methods are importantaspects of these efforts.
Halichondrin B (1) is a structurally complex substance isolated from a Pacific sponge. Potent cytotoxicity in vivo against leukemias and solid tumors in mice combines with extreme scarcity to encourage laboratory synthesis of this and analogous structures for development as clinical anticancer agents. Early efforts from our labs toward the halichondrins are described in reference 7. Breynogenin (2) is the aglycon of a novel substance that lowers serum cholesterol levels. It structurally resembles the antitumor agent phyllanthoside, the aglycon of which we have synthesized (reference 1). Hypocholesterolemic agents are among the most important classes of drugs for the prevention of heart disease. Our efforts directed at breynogenin were preceded by the synthesis of compactin, another type of cholesterol-lowering agent (reference 8). Many natural antibiotics facilitate the transport of ions across biological membranes. Polysubstituted hydropyrans (see reference 3) are commonly present in these polyether and ionophore antibiotics, and we have developed versatile and complementary routes to these heterocycles. Incorporation of these subunits into macrocyclic hydropyran oligolides with 12-, 14-, 18-, 21-, 28-, 36-, 48- and 54-membered rings has provided a new class of ion transport agents. These optically pure macrocycles are being developed as templates for membrane-spanning channels analogous to those employed by living organisms. Several of these macrocycles have also been shown to form solid-state inclusion complexes (clathrates) with neutral molecular guests.
The eighteen membered macrolide (3) and the similar macrolide/KSCN complex (4) are representative of the many examples we have synthesized via efficient reiterative and self-assembly procedures. Design, preparation and study of a new generation of these functional molecules is underway. Crystallographic, spectroscopic, ion transport, and complexation studies are revealing fundamental qualitative aspects of host-guest relationships. Central to all of our projects is the ability to build, purify and characterize exotic organic structures. Diverse exposure to mechanistic, analytical, computational, spectroscopic and chromatographic techniques will be part of your training. Organometallic and biological chemistry are also pertinent to these studies. If you are interested in a career in pharmaceutical drug discovery and development, the research background available through these projects is considered to be ideal. Last updated February 28, 2001.
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