Abstract

3D Chemical Scaffold Mimics from Biologically Active Natural Products

Mark Moloney, Professor of Chemistry, University of Oxford

The desire to identify new chemical matter suitable for rapid development in the drug discovery process has led to an interest in 3D chemical scaffolds. Our focus has been on the use of antibacterial natural products containing pyroglutamate and tetramate core structures, and using these as inspiration, we have developed novel chemistry that uses suitable serine, threonine, cysteine and pyroglutamate-derived chiral 3D templates for rapid diasteroselective and enantioselective synthesis. Although simple unsubstituted pyrrolidines and tetramates appear to be intrinsically devoid of activity, application of these templates for fragment-based synthesis, has permitted access to several compound series which possess high levels of antibacterial activity, suggesting that mimics of natural products might fast track the identification of bioactive chemical libraries.