INTERMEDIATES FOR ORGANIC SYNTHESIS

有机合成中间体

• 批准号: 2178181
• 负责人: Paul G. Williard
• 金额: $ 27.11万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178181
• 关键词: X ray crystallography; chemical models; chemical structure; chemical synthesis; drug design /synthesis /production; enolate; nuclear magnetic resonance spectroscopy; stereochemistry

The principal aim of the research program set forth in this application is to obtain structural information about reactive intermediates in organic chemical reactions. These structural results are invaluable for the development of new synthetic methodology. I particular, the stereoselectivity of common organic reactions is of utmost concern and importance in the design of chemical syntheses of every small organic molecule that is listed in publications such as the NCI publication Chemical Structures of Interest to the Division of Cancer Treatment. The structural information obtained in this research program will permit the rational design of new synthetic reactions and will also yield improved efficiency in organic synthesis. Since a stated goal of the NIH is to obtain chemical compounds for screening as well as for utilization in clinical trails, and since a large number of compounds on the current list of compounds used in clinical trials and in earlier stages of development by the NIH are prepared by organic chemical synthesis, it is extremely important that efficient and useful processes exist for the preparation of such compounds. The research proposed herein will greatly assist with the ongoing development of synthetic organic chemistry leading to the synthesis of physiologically active, small organic molecules. the efficiency of total syntheses of both naturally occurring and non-naturally occurring analogs of such compounds will be improved thorough understanding of the intimate structural details of the reactive intermediates involved in the synthesis of such compounds. Synthetic methodology will be proposed and developed as a consequence of the structural results. The structural results will be obtained by utilizing the techniques of NMR spectroscopy, x-ray diffraction analysis and computional chemistry. The structural results generally are presented as three dimensional representations of aggregated species formed as reactive intermediates is almost all synthetic reactions involving carbanions. This structural information will be utilized to design models to explain and to predict the stereospecificity of organic chemical reactions. Additionally, the structural information will be utilized to develop and to improve new synthetic reagents for the asymmetric synthesis of physiologically active organic molecules. Hence, the structural work will be accompanied by experimental work on the development of new asymmetric reactions for use in the total synthesis of physiologically active compounds.

本申请中提出的研究计划的主要目的 是为了获得有关反应中间体的结构信息 有机化学反应。 这些结构性结果对于 新合成方法的发展。 我特别指出， 常见有机反应的立体选择性是最受关注的 在每种小型有机物的化学合成设计中的重要性 NCI 出版物等出版物中列出的分子 癌症治疗部门感兴趣的化学结构。 这 在本研究计划中获得的结构信息将允许 合理设计新的合成反应，收率也会提高 有机合成效率。 由于 NIH 的既定目标是 获得用于筛选和利用的化合物 临床试验，并且由于目前有大量化合物 用于临床试验和早期阶段的化合物清单 由美国国立卫生研究院 (NIH) 开发，通过有机化学合成方法制备， 极其重要的是，存在高效且有用的流程 此类化合物的制备。 本文提出的研究将极大 协助合成有机化学的持续发展 导致具有生理活性的小有机物的合成 分子。 天然存在的两种物质的全合成效率 以及此类化​​合物的非天然类似物将得到改进 彻底了解反应性的密切结构细节 参与此类化合物合成的中间体。 综合方法论将被提出并发展 结构结果。 结构结果将通过以下方式获得 利用核磁共振波谱、X射线衍射分析技术 和计算化学。 结构结果一般是 呈现为聚合物种的三维表示 几乎所有合成反应均以反应中间体形式形成 涉及碳负离子。 该结构信息将用于 设计模型来解释和预测有机物的立体特异性 化学反应。 此外，结构信息将是 用于开发和改进新的合成试剂 生理活性有机分子的不对称合成。 因此， 结构工作将伴随着实验工作 开发用于全合成的新不对称反应 生理活性化合物。