NATURAL PRODUCT SYNTHESES

该研究计划旨在开发有机合成的新方法， 将其应用于生物活性天然产物的合成， 类似物 具有潜在生物活性的结构 将准备适当数量的测试，通过 国家癌症研究所和康奈尔兽医学院。 重点介绍了新型过渡金属试剂和电化学 技术. 特异性靶分子包括醌类抗生素 例如石榴皮素，其中关键步骤将涉及卡宾-金属络合物， 和离子型抗生素，如四环霉素，其中至关重要的呋喃和 吡喃环将用钯催化的方法选择性地形成。 其他离子载体和大环内酯类抗生素的关键部分， 控制相邻手性中心的立体关系，将是 合成了 将开发基本的新氧化方法，使用 电化学来重新循环关键试剂。 长期目标是 一组基于胺的电极负载型氧化催化剂。 耦合 是有机合成中最基本的问题， 将开发基于镍和铁的低价金属试剂。 电还原将被用来再生活性催化剂。 总的来说，这一努力将使可用性更强大，更有选择性 药物合成的工具，并将定义特定的途径， 药物开发中当前感兴趣的分子。

The research plan aims to develop new methods of organic synthesis and apply them in the synthesis of biologically-active natural products and analogs. Structures with potentially interesting biologically activity will be prepared in appropriate quantities for testing, through the National Cancer Institute and the Cornell Veterinary College. The emphasis is on new transition-metal reagents and electro-chemical techniques. Specific target molecules include quinone-based antibiotics such as granaticin, where key steps will involve carbene-metal complexes, and ionophone antibiotics such as tetronomycin, where crucial furan and pyran rings will be formed selectively with palladium-catalyzed processes. Key sections of other ionophore and macrolide antibiotics, with carefully controlled stereo-relationships of adjacent chiral centers, will be synthesized. Basic new oxidation methods will be developed, using electro-chemistry to re-cycle the key reagents. The long range goal is a set of electrode-supported oxidation catalysts based on amines. Coupling of two carbon units is the most fundamental problem in organic synthesis, and low valent metal reagents based on nickel and iron will be explored. Electro-reduction will be employed to regenerate the active catalysts. Overall, this effort will make available more powerful and more selective tools for drug synthesis, and will define specific pathways to classes of molecules of current interest in drug development.