In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Simon Blakey of Emory University is developing new reactions that will allow the synthesis of two novel families of bioactive molecules. The development of new methodology, and the demonstrated ability to access multiple classes of natural products that were previously inaccessible, will set the stage for further understanding of the basic biological activities of these molecules. This fundamental research will pave the way for the development of the therapeutic properties implied in ethnomedicine studies that serve as the inspiration for this project, furthering our understanding of malarial resistance to common drug treatments, and potentially providing a road map to new clinical entities.
An outreach program is exploring the narrative of the malagashanine story through a collaboration between the sciences and the arts. The combination illustrates the interplay between disciplines to inform a public audience on cutting edge science and ethical questions arising from the discoveries. Professor Blakey will deliver public lectures at the Atlanta Botanical Garden, and ultimately to broad audiences as part of the Atlanta Science Festival.
The unusual structures of these molecules render them difficult to synthesize with existing methods. To date, no members of either family have been synthesized. To meet the challenge posed by these molecules, and provide significant quantities for further biological study, new reactions and new catalysts to control these reactions are under development. Specifically, a series of stereospecific iminium ion initiated cascade reactions, and novel chiral disulfonamide catalysts will be developed and studied, providing solutions to the synthetic problem posed by the malagashanine and akuamma alkaloids. These studies are expected to culminate in the syntheses of representative molecules from both families.
