TBKO · Synthesis and Biological Evaluation of a Potent Antituberculosis Natural Product and Analogues

This project is directed toward the total synthesis and full structural elucidation of an epidithiodiketopiperazine natural product endowed with highly potent antituberculosis properties and whose full structure and biological evaluation remain incomplete due to its natural scarcity. The proposed research program also includes design, synthesis and biological evaluation of novel analogues of the target molecule as part of an optimization effort, and attempts to identify its biological target.The first year of research and training will be conducted under the supervision of Prof. K.C. Nicolaou (Rice, USA), where the synthesis and compound characterization part of the project will be pursued. In the return phase, the applicant will go to Geneva to work under the supervision of Prof. N. Winssinger (University of Geneva, Switzerland) where the synthesis of the analogues will be performed. The compounds synthesized will be tested for biological activities and evaluated for growth inhibition in a panel of mycobacteria (screeni available through Prof T. Soldati at Geneva).