Dale L. Boger, PhD

Synthetic Organic Chemistry and Chemical Biology. Our research interests include the total synthesis of natural products, development of new synthetic methodology, bioorganic and medicinal chemistry, heterocyclic chemistry, the study of DNA-agent interactions, and the chemistry of antitumor agents and antibiotics. We place special emphasis on investigations to define the structure-function relationships of natural or designed agents.

Synthetic Methodology. Our ongoing investigations emphasize the development and application of hetero Diels-Alder reactions, the thermal reactions of cyclopropenone ketals, inter- and intramolecular acyl radical-alkene addition reactions, medium and large ring cyclization methods, and MHAT chemistry. In each instance, the methodology development represents the investigation of chemistry projected as a key step in the total synthesis of a natural or nonnatural product.

Natural Products Total Synthesis. Problems recently or currently being addressed include vinblastine, vincristine, duocarmycins (antitumor antibiotics possessing sequence selective DNA alkylation properties), vancomycin, teicoplanin, ristocetin, chloropeptins, ramoplanin, bleomycin A2 (clinically employed antitumor agent), quinolinequinone antitumor antibiotics including streptonigrone, streptonigrin, and lavendamycin, fostriecin, cytostatin, and phostriecin.

Bioorganic Chemistry. The orgin of interest in the compounds detailed above rests with their properties and in many instances represent the selection of compounds related by a projected property (e.g., vancomycin, (+)-CC-1065 and duocarmycin). Representative of such efforts is the redesign of the core structure of vancomycin and its peripheral modification to provide potent antibiotics that act by up to three mechanisms of action and overcome antibiotic resistance.

Collaborative efforts in securing biological data, NMR of the compounds in complex with their targets, molecular modeling studies of large molecule-small molecule interactions, and experimental studies of their interactions constitute an integral part of the program.