SYNTHETIC STUDIES OF LITHIATED HETEROCYCLES

锂杂环的合成研究

• 批准号: 2910359
• 负责人: ROBERT E. GAWLEY
• 金额: $ 23.87万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2910359
• 关键词: chemical synthesis; lithium; nitrogenous heterocyclic compound

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.

描述：（主要调查员）许多（如果不是大多数） 当今（全球）使用的药物是氮杂环。 我不太可能在下一个情况下发生巨大变化 十年，因此对这种物种的新化学反应的持续调查是 有保证，因为它提供了合成的新方法，理解 化学反应性和新颖化合物。 其中概述了 提案寻求充分发展有关该问题的最新基本发现 固定的氮杂环的化学和合成效用。 这 这些研究中获得的知识有望增强我们的能力 合成含有氮杂环的复合物分子 有效的方式。 一位当局最近断言“与有机锂的反应 物种作为试剂，反应物或中间体的建立得很好 该组织矿是当代最广泛使用的有机金属 组织化学”（Beak等人，Acc。Chem。Res。1996，29，552-560）。 拟议的机械研究将提供基本和基本知识 关于有机矿越来越重要的一类有机矿 综合，THA将产生超出直接问题的影响 在此处。 该提案的具体目的是：（1）继续 研究α-氨基矿石的范围和局限性 烷基化和乙状结肠重排，重点 立体选择性。 开发改进的方法o准备。 （2）应用 n- allyl-2-lithio杂环与合成的sigmatropic重排 AZA糖和潜在的糖苷酶抑制剂。 （3）使用光谱学 和冷冻镜技术，表征了TH的溶液结构 未稳定的α-氨基岩种类。 尝试t种晶体 X射线衍射分析。 （4）检验的假设是 α-氨氨基岩的偶尔非选择性反应是DU 单电子传输过程的干预。