The complexity and structural richness of natural products has inspired medicinal and organic chemists for many years. A new chapter in the field has opened wherein scientists are using nature's inspiration as a starting point for the design of new natural productlike libraries. Two CMLD projects that use this approach are directed by Professor Brian Blagg, of the KU Department of Medicinal Chemistry, and Professor Keith Buszek, of the Chemistry Department at the University of Missouri-Kansas City. Blagg's group is interested in compounds that interact with the 90 kDa heat shock proteins (Hsp90), which are essential chaperones required for the refolding of denatured proteins and the folding of nascent polypeptides into their biologically active, three-dimensional structures. Examples include geldamycin and radicicol. Buszek's laboratory is involved in making analogs of the eight-membered lactone natural product and powerful antitumor agent octalactin A. Both projects involve the development of new synthetic methodology as well, including polymer-bound olefination reagents and the use of ring-closing metathesis for the synthesis of medium rings.
"Privileged structures" are molecular subunits that are associated with a high degree of biological activity across more than one pharmacological target. One such set of structures being investigated by Professor Gunda I. Georg's group, of the University of Kansas Medicinal Chemistry Department, are the quinolones. Quinolones of various kinds have been associated with antimicrobial or anticancer activity. The Georg group has developed a new heterocyclization route to quinolones that can be readily diversified into libraries of new quinoline derivatives.
