Synthetic Pyridinium Salt Photochemistry

该研究项目致力于开发新的合成方法，这些方法可应用于设计用于制备生物医学上重要目标的简明路线。这项研究建立在近30年前发现的一个有趣的吡啶盐光环化反应的基础上，该反应将转化为一种有效的方法，用于立体控制合成高度功能化的氨基环戊烯。我们将通过对融合吡啶和聚缩合n -杂芳烃盐的光化学反应的探讨来探讨这种光环化反应的普遍性。研究了n链碳水化合物助剂和手性链对吡啶盐光环化反应的绝对立体化学控制。立体控制吡啶盐光环化反应将作为短序列合成强效海藻化酶抑制剂(+)-trehazoline、蛋白酶体抑制剂(+)-lactacystin、糖苷酶抑制剂(+)-castanospermine、uniflorine-A及相关的多羟基吲哚嘧啶和喹啉嘧啶的关键步骤。有了这个奖项，有机和大分子化学项目支持了新墨西哥大学化学系的帕特里克·s·马里亚诺博士的研究。马里亚诺教授和他的学生正在探索光驱动（“光化学”）反应作为潜在的工具来影响各种有机分子的受控合成。调查集中在合成方法的发展，但它更广泛地设计来解决与生物医学上重要目标的合成和在光化学过程中形成的高能中间分子的化学有关的问题。该项目将对合成有机化学领域做出总体贡献，同时对化学教育产生同样重要的影响，该项目将为学生提供广泛而全面的基础。

This research program addresses the development of novel synthetic methods that can be applied to the design of concise routes for the preparation of biomedically important targets. The investigations build on an intriguing pyridinium salt photocyclization reaction, discovered nearly 30 years ago, which will be transformed into a potent methodology for the stereocontrolled synthesis of highly functionalized aminocyclopentenes. The generality of this photocyclization reaction will be probed through an exploration of the photochemistry of fused-pyridinium and polycondensed N-heteroaromatic salts. Absolute stereochemical control of the pyridinium salt photocyclization reactions by N-linked carbohydrate auxiliaries and chiral tethers will be also investigated. Stereocontrolled pyridinium salt photocyclization reactions will be used as key steps in short sequences for the synthesis of the potent trehalase inhibitor (+)-trehazoline, the proteasome inhibitor (+)-lactacystin, and the glycosidase inhibitors (+)-castanospermine, uniflorine-A and related polyhydroxylated indolizidines and quinolizidines.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Patrick S. Mariano, of the Department of Chemistry at the University of New Mexico. Professor Mariano and his students are exploring light-driven ("photochemical") reactions as potential tools to effect the controlled synthesis of various classes of organic molecules. The investigation concentrates on synthetic methodology development, but it is more broadly designed to address issues that relate to the synthesis of biomedically important targets and the chemistry of the high energy intermediate molecules formed in photochemical processes. General contributions will be made to the field of synthetic organic chemistry, while equally significant is the impact that the studies will have on chemical education, with this project providing a broad, comprehensive foundation for students.