Total Synthesis of Anti-Cancer Natural Products

本课题旨在利用化学合成方法制备四类具有巨大潜力的抗癌天然产物，这些天然产物由于其在自然界的稀缺性和化学合成方法的缺乏而无法研究。实际合成维尼格罗、毛晶体、卡帕卡因、肉毒杆菌素和相关家族成员将需要发展新的合成方法，以及探索新的化学实体和反应模式。此外，计划通过精心设计的类似物的合成来彻底探索它们的生物学。从化学和生物学的角度来看，这些天然产物家族中的每一个都是理想的目标。在化学上，它们挑战了目前的技术水平，需要创新的解决方案来完成实际的全合成。它们通过尚不清楚的机制引起生物影响，因此有可能阐明基本的生物化学过程。最后，它们被赋予了强大的生物活性，可以想象进入临床环境。通过与癌症生物学领域的几位领导者的战略合作，预计化学领域的新策略和方法以及对医学的重大贡献。

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.