NEW DEVELOPMENTS IN ORGANOCOPPER CHEMISTRY

有机铜化学的新进展

基本信息

批准号：
6882358
负责人：
R Karl KARL DIETER
金额：
$ 5.29万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-02-01 至 2006-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6882358
关键词：
chemical synthesis copper nitrogenous heterocyclic compound organometallic compounds stereochemistry

项目摘要

The specific aim of the proposed work is to develop the chemistry of alpha-aminoalkylcopper reagents; a type of organocopper reagent that permits functionalization alpha to an amino group using the reactions characteristic of organocopper reagents. The specific objectives are to (1) expand the range of cuprate-electrophile reaction partners, (2) explore the reactivity and thermal stability of these reagents, and the configurational stability of cuprates with a C-Cu stereogenic center, (3) optimize reaction conditions, substrates, and reagents for effecting relative (diastereoselectivity) and absolute (enantioselectivity) asymmetric induction in the characteristic reactions of alpha-aminoalkylcuprates, and (4) develop the synthetic utility of these reagents by developing synthetic strategies for the synthesis of highly substituted 5-membered heterocyclic compounds with a focus on the pyrrolidine aza sugars. The synthetic approach to highly substituted pyrrolines, pyrrolidines, and pyrrolidinones involves the reaction of alpha-aminoalkylcuprates with scalemic propargyl substrates in a controlled anti-SN2' process followed by cyclization of the carbamate nitrogen or free amine onto the resultant allene. The work will extend the scope and synthetic utility of these organocopper reagents. Successful development of alpha-aminoalkylcuprate chemistry will contribute significantly to the synthesis of highly substituted pyrrolidines, piperidines, and their bicyclic analogs (i.e., pyrrolizidines, indolizidines, and quinolizidines). Complex alkaloids and simple nitrogen-containing compounds are biologically active agents representing important classes of antibacterial agents, CSN agents, and antiretroviral compounds. The polyhydroxy analogs (i.e., aza sugars) are an important class of glycosidase inhibitors and immunostimulators and are the focus of intense synthetic activity because of their effects upon glycoprotein processing enzymes. Inhibition of glycoprotein processing is potentially useful against illnesses such as cancers, malaria, diabetes, cystic fibrosis, bacterial, and viral infections including retro-viruses such as the human immunodeficiency virus (HIV). A need exists for a general synthetic approach to the aza sugars that is short, efficient, and which divergently leads to a large number of stereoisomers and analogues from a common intermediate. The proposed synthetic routes to pyrrolidine aza sugars will develop the potential synthetic power of alpha-aminoalkylcuprate chemistry.

拟议工作的具体目的是开发α-氨基烷基copper试剂的化学。一种使用Orangopper试剂的反应特征的有机体试剂，允许使用功能化alpha到氨基组。特定目标是（1）扩大库酸酯 - 电动反应伴侣的范围，（2）探索这些试剂的反应性和热稳定性，以及用C-CU立体源性中心的铜层的构型稳定性，（3）优化对反应条件的优化，对效应相对（ASSTEREECELECTIONTIS）的反应条件，并构成了反应条件，并具有良好的特征（ASSTERECOLECTIONTION）（ASSTERECELITION），并构成了特征。 α-氨基烷基化的反应以及（4）通过开发合成策略来合成高度取代的5元杂环化合物，从而开发这些试剂的合成效用，重点是吡咯烷酸AZA糖。高度取代的吡咯，吡咯烷和吡咯烷酮的合成方法涉及在受控的抗SN2'过程中α-氨基烷基化的反应与鳞状proparyl底物在受控的抗Sn2'过程中的反应，然后通过氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基转移。这项工作将扩大这些有机肥料试剂的范围和合成效用。成功发展α-氨基烷基化学化学将显着促进高度取代的吡咯烷，哌啶及其双环类似物（即吡咯烷，吲哚胺，吲哚胺和喹啉苷）的合成。复杂的生物碱和简单的含氮化合物是代表重要类别的抗菌剂，CSN剂和抗逆转录病毒化合物的生物活性剂。多羟基类似物（即AZA糖）是一类重要的糖苷酶抑制剂和免疫刺激剂，并且是强大合成活性的重点，因为它们对糖蛋白加工酶的影响。糖蛋白加工的抑制可能对癌症，疟疾，糖尿病，囊性纤维化，细菌和病毒感染等疾病有用，包括人类免疫缺陷病毒（HIV）。需要对较短，高效的AZA糖的一般合成方法，并且会导致大量的立体异构体和类似物与普通中间体。提出的吡咯烷AZA糖的合成途径将发展出α-氨基烷基化学的潜在合成能力。