Kingston David G I
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
J Org Chem. 2008 Jun 6;73(11):3975-84. doi: 10.1021/jo800239a. Epub 2008 May 7.
Recent research on the chemistry of natural products from the author's group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery.
本文回顾了作者团队近期在天然产物化学领域的研究，该研究使作者团队获得了美国化学学会天然产物化学领域的欧内斯特·京特奖。REDOR核磁共振和合成研究确定了T-紫杉醇构象为具有生物活性的微管蛋白结合构象，并且通过合成化合物证实了这些结果，这些化合物的活性与否显然取决于它们是否能够采用T-紫杉醇构象。对埃坡霉素的类似研究表明，目前的微管蛋白结合模型需要修改。文中还列举了在苏里南和马达加斯加发现天然产物及保护生物多样性的实例，并得出结论：天然产物化学将继续为药物发现做出重大贡献。
