Dr. Brendan Crowley, Sloan Kettering

Synthesis and re-engineering of complex natural products with significant biological activities

Natural products have been utilized effectively in the treatment of numerous human diseases. Subtle structural modifications of chemotherapeutic agents can lead to increased potency, decreased side effects, and enhanced bioavailability. While great advances have been made in the "editing" of natural products through the alteration of biosynthetic pathways, the complementary discipline of chemical synthesis remains a powerful method for preparing new molecular entities. The majority of this talk will describe the synthesis and reengineering of vancomycin-group antibiotics, powerful agents for the treatment of Gram-positive bacteria such as MRSA, to be effective against vancomycin-resistant strains. The development of total and semi-synthetic methods for the modification of the aglycon portions of these molecules will be discussed. The remainder of the time will focus on the employment of underutilized synthetic methods for the construction of the novel indole-alkaloid actinophyllic acid, a potential agent for the treatment of thrombotic disorders. This section will delve into the unique organic chemistry challenges presented by this cage-like natural product that possesses an unprecedented structure.

For more information contact: Dr. Stefan France (404-385-1796).