Total Synthesis of Anti-Cancer Natural Products

Scripps Research Institute, The, La Jolla CA

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Abstract

This proposal aims at using chemical synthesis to prepare four classes of anticancer natural products with great potential that have eluded study due to their scarcity in nature and the fact that no solution for their chemical synthesis exists. Practical syntheses of vinigrol, maoecrystal, kapakahine, sarcodonin, and related family members will require the development of new synthetic methodologies, as well as the exploration of novel chemical entities and reactivity patterns. In addition, a thorough exploration of their biology through the synthesis of carefully designed analogs is planned. Each of these natural product families represent ideal targets from both a chemical and biological perspective. Chemically, they challenge the state of the art and require innovative solutions in order to accomplish their practical total synthesis. They elicit their biological influence through as yet unknown mechanisms and thus have the potential to shed light on fundamental biochemical processes. Finally, they are endowed with potent bioactivity and could conceivably enter into a clinical setting. New strategies and methods in chemistry and substantial contributions to medicine are anticipated through strategic collaborations with several leaders in the field of cancer biology.