SYNTHETIC STUDIES OF LITHIATED HETEROCYCLES

描述：(首席调查员)许多，如果不是大多数的话， 当今(全世界)使用的药剂是含氮杂环。 在接下来的一年里，这种情况不太可能发生巨大的变化 十年，因此对这类物种新化学的持续研究 保证，因为它提供了新的合成方法，理解 化学反应和新化合物。这篇文章中概述的研究 一项提案寻求充分发展最近关于 锂氮杂环化合物的化学和合成用途。这个 从这些研究中获得的知识可望增强我们的能力 一种合成含氮杂环复杂分子的方法 高效的方式。 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种是如此成熟 有机锂是当代应用最广泛的有机金属 《有机化学》(Beak et al，Acc.Chem.Res.1996，29,552-560)。 拟议的机械学研究将提供基本和基本的知识 关于一类对有机化合物日益重要的有机锂化合物 综合，而THA将产生超越眼前问题的影响 在这里。这项建议的具体目的是：(1)继续 α-氨基有机锂的应用范围和局限性研究 烷基化和顺式重排，重点是 立体选择性。开发改进的制备方法。(2)适用于 N-烯丙基-2-锂杂环的S型重排反应 氮杂糖和潜在的糖苷酶抑制剂。(3)使用光谱分析 和冷冻技术，表征了溶液的结构 不稳定的α-氨基有机锂物种。尝试生长晶体以用于 X射线衍射分析。(4)检验以下假设： α-氨基有机硫的偶发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.