INVESTIGATION OF INTERMEDIATES FOR ORGANIC SYNTHESIS

有机合成中间体的研究

基本信息

批准号：
3289535
负责人：
Paul G. Williard
金额：
$ 13.71万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-01-01 至 1993-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3289535
关键词：
X ray crystallography antineoplastics cardiotonic agents chemical synthesis drug design /synthesis /production drug screening /evaluation enolate nuclear magnetic resonance spectroscopy stereochemistry stereoisomer terpenes

项目摘要

The principal aim of the research program set forth in this application is to improve the methodology currently employed to synthesize compounds with physiological activity. In particular, the stereoselectivity (both enantioselectibility and regioselectivity) of common organic reactions is of major concern in the preparation of many of the compounds listed in the NCI publication Chemical Structures of Interest to the Division of Cancer Treatment. Since a number of the compounds on the current list of chemical compounds used in clinical trials or in earlier stages of development are prepared by; chemical synthesis, it is important that efficient and useful processes exist for the preparation of these compounds in vitro. The work outlined herein will greatly assist with the ongoing development of synthetic routes to a number of the compounds of interest to the National Cancer Institute. In addition, the total syntheses of non- naturally occurring analogy of these compounds may be more easily prepared by carefully consideration of the results of this research. In light of the increasing emphasis placed upon the search for enantiospecific organic reactions, a proposal to improve the efficiency of enantiospecific reactions is presented. This goal will be pursued by structural investigations, both by NMR and x- ray diffraction analyses, of the common reactive intermediates thought to be involved in the reactions. The structural information will be utilized to devise models to explain and to predict the stereoreactivity of the reactive intermediates. Additionally, the structural information obtained herein will be used to devise and to develop new synthetic reagents for asymmetric synthesis of organic molecules. The structural work will be followed up by experimental work on the development of new asymmetric reactions for use in the total synthesis of physiologically active compounds.

本研究计划的主要目标应用程序是为了改进目前采用的方法合成具有生理活性的化合物。尤其，立体选择性（对映选择性和常见有机反应的区域选择性）是主要关注点用于制备 NCI 中列出的许多化合物出版物《化学结构的兴趣划分》癌症治疗。由于目前的许多化合物用于临床试验或早期的化合物清单开发阶段的准备工作是：化学合成，它是重要的是，存在有效且有用的流程这些化合物的体外制备。本文概述的工作将极大地促进合成材料的持续发展通往国家感兴趣的许多化合物的路线癌症研究所。此外，非全合成这些化合物的天然存在的类似物可能更容易经过认真考虑本次调查结果而制定研究。鉴于人们越来越重视寻找对映特异性有机反应，改进的建议提出了对映特异性反应的效率。这个目标将通过 NMR 和 x- 进行结构研究常见反应中间体的射线衍射分析被认为参与了反应。结构性信息将被用来设计模型来解释和预测反应中间体的立体反应性。此外，本文获得的结构信息将是用于设计和开发新的不对称合成试剂有机分子的合成。结构工程将是随后开展新产品开发的实验工作用于全合成的不对称反应生理活性化合物。