Our total synthesis targets include several families of polycyclic pyrrolidine, piperidine, and guanidine alkaloids, which exhibit a wide array of biological activities including, inter alia, antitumor, antiviral, antibacterial, and antinociceptive properties. In order to realize the therapeutic potential of this broad collection of natural products, as well as to probe their varied mechanisms of biological activity, efficient strategies for their chemical construction need to be developed. All of these syntheses focus on strategic development and application of a variety of hetero-annulation reactions.
Within this alkaloid total synthesis program is the potential for the discovery of novel biological probes and therapeutics beyond structure-activity-relationship studies of the natural products themselves. Implicit in our total synthesis efforts is the generation of a compound collection with a dimension of diversity spanning a variety of molecular scaffolds. In collaboration with the state-of-the-art high throughput screening (HTS) facility at MSKCC, testing of all unique synthetic intermediates derived from our synthetic efforts against a panel of known cancer cell lines are underway for novel drug discovery.