NATURAL PRODUCT SYNTHESES

该研究计划旨在开发新的有机合成方法和 将其应用于生物活性天然产物的合成和 类比。具有潜在生物活性的结构 将准备适当数量的材料用于测试，通过 国家癌症研究所和康奈尔兽医学院。 重点是新的过渡金属试剂和电化学 技巧。特定的靶标分子包括基于苯醌的抗生素 例如颗粒素，其中关键步骤将涉及卡宾-金属络合物， 以及离子体类抗生素，如四诺霉素，在这些抗生素中，关键的呋喃和 在钯的催化作用下，吡喃环将被选择性地形成。 其他离子载体和大环内酯类抗生素的关键部分，要小心 相邻手性中心的受控立体关系将是 合成的。将开发基本的新氧化方法，使用 电化学法重新循环关键试剂。远距离的目标是 一套以胺为基础的电极支载氧化催化剂。偶联 两个碳单元的平衡是有机合成中最基本的问题， 并将探索以镍和铁为基础的低价金属试剂。 采用电还原的方法对活性催化剂进行再生。 总体而言，这一努力将使可用的功能更强大，更具选择性 用于药物合成的工具，并将定义具体的途径，以达到 目前在药物开发中感兴趣的分子。

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.