|Name||Mr. Verrill Norwood IV|
|Organization||University of Florida-Department of Medicinal Chemistry|
Complexity-to-Diversity on the Indole-Containing Natural Product Vincamine
Verrill M. Norwood IV and Robert W. Huigens III
Department of Medicinal Chemistry; College of Pharmacy, University of Florida
Despite the rich history of natural products as sources of bioactive molecules, the 1990s saw a paradigm shift away from natural products and toward the screening of collections of synthetic compounds (i.e. High-Throughput Screening (HTS)). This paradigm shift is due to many factors, including the increasing difficulty of identifying new natural products, the ease of sp2-sp2 coupling reactions, and the rise of combinatorial and parallel synthesis methodology used to rapidly generate large compound libraries. Consequently, current drug screening libraries are highly populated with flat (e.g. sp2 hybridized) molecules. These screening libraries have been effective at targeting protein targets with flat binding pockets (e.g. protein kinases), but ineffective against more complex biological targets (e.g. protein-protein interactions). To address this lack of complexity, the complexity-to-diversity (CtD) approach can be utilized; commercially available natural products are used to create diverse screening libraries.6 Herein we report the CtD method used on the indole-containing natural product vincamine. Currently, our vincamine library is being screened at the Center for Natural Products, Drug Discovery and Development (CNPD3).