SYNTHETIC STUDIES OF LITHIATED HETEROCYCLES

描述：（主要研究者的）许多，如果不是大多数， 当今（世界范围内）使用的药物是氮杂环。 这种情况不太可能在未来几年内发生急剧变化。 十年，因此继续研究这些物种的新化学物质是必要的。 有必要，因为它提供了新的合成方法， 化学反应性和新化合物。 本文中概述的研究 该提案旨在充分发展最近的基本发现 锂化氮杂环的化学和合成应用。 的 从这些研究中获得的知识有望提高我们的能力， 合成含氮杂环化合物， 有效方式 一位权威人士最近断言，“与有机锂的反应 作为试剂、反应物或中间体的物质是如此确定 有机锂是当代最广泛使用的有机金属化合物， 有机化学”（Beak等人，Acc.Chem.Res.1996，29，552-560）。 的 拟议的机制研究将提供基本和基础知识 关于一类有机锂， 综合，而《战略行动纲领》的影响将超出所提出的直接问题 本文所 本提案的具体目标是：（1）继续 α-氨基有机锂的范围和局限性的研究 烷基化和σ迁移重排，重点是 立体选择性 开发改进的制备方法。 (2)应用 N-烯丙基-2-锂杂环的σ转移重排反应 氮杂糖和潜在的糖苷酶抑制剂。 (3)使用光谱 和冰点下降技术，表征了溶液结构， 不稳定的α-氨基有机锂物质。 尝试生长晶体 X射线衍射分析。 (4)测试假设， α-氨基有机锂的偶然非选择性反应是由于 单电子转移过程的干预。

DESCRIPTION: (Principal Investigator's) Many, if not most, of the pharmaceutical agents in use today (worldwide) are nitrogen heterocycles. It i unlikely that this situation will change drastically in the next decade, so continuing investigation of new chemistry in such species is warranted, insofa as it provides new methods of synthesis, understanding of chemical reactivities, and novel compounds. The studies outlined in this proposal seek to fully develop recent fundamental discoveries about the chemistry and synthetic utility of lithiated nitrogen heterocycles. The knowledge gained in these studies is expected to enhance our ability to synthesize complex molecules containing nitrogen heterocycles in an efficient manner. One authority has recently asserted that "Reactions with organolithium species as reagents, reactants, or intermediates are so well established that organolithiums are the most widely used organometallics in contemporary organi chemistry" (Beak et al, Acc. Chem. Res. 1996, 29, 552-560). The proposed mechanistic studies will provide basic and fundamental knowledge about a class of organolithiums that are of growing importance to organic synthesis, and tha will have an impact beyond the immediate questions posed herein. The specific aims of this proposal are to: (1) Continue investigation of the scope and limitations of alpha-aminoorganolithium alkylations and sigmatropic rearrangements, with emphasis on stereoselectivity. Develop improved methods o preparation. (2) Apply the sigmatropic rearrangement of N-allyl-2-lithio heterocycles to the synthesis of aza sugars and potential glycosidase inhibitors. (3) Using spectroscopic and cryoscopic techniques, characterize th solution structure of unstabilized alpha-aminoorganolithium species. Attempt t grow crystals for X-ray diffraction analysis. (4) Test the hypothesis that the reason for occasional nonselective reaction of alpha-aminoorganolithiums is du to the intervention of single electron transfer processes.