Catalytic Asymmetric Reductive Coupling Reactions to Prepare Bioactive Molecules

催化不对称还原偶联反应制备生物活性分子

基本信息

批准号：
8887353
负责人：
Sarah Elizabeth Reisman
金额：
$ 29.31万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-15 至 2016-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The overarching goal of this proposal is to develop new nickel-catalyzed enantioselective reductive cross- coupling reactions for applications in the synthesis and study of bioactive molecules. It is well established that the two enantiomers of a drug can exhibit remarkably different biological properties. As a result, the enantioselective synthesis of chiral small molecules has become an important area of research in both academic and industrial laboratories. Recently, Nickel-catalyzed reductive cross-coupling reactions have emerged as direct methods for carbon-carbon bond formation. These reactions typically tolerate an array of functional groups, occur under mild conditions, and employ inexpensive, earth abundant metals as stoichiometric reductants. Most importantly, they do not require the use of pre-generated organometallic reagents. In order to realize the full synthetic potential of Ni-catalyzed reductive cross-coupling reactions, it is critical to develop enantioselective variants o these transformations. This proposal describes the first significant progress toward this objective: the development of four new Ni-catalyzed enantioselective cross- coupling reactions. Preliminary results obtained for each transformation provide compelling evidence for the feasibility of this research. This research will be carried out by a team composed of the PI, three chemistry graduate students and one postdoctoral researcher. As part of this project, the graduate students and postdoctoral researchers will receive rigorous training in the theory, methods, and strategies of organic chemistry. The successful execution of this research will provide new tools to enable the synthesis of small molecules for the study and treatment of human disease.

描述（由申请人提供）：该提案的总体目标是开发新的镍催化对映选择性还原性还原交叉偶联反应，以用于在生物活性分子的合成和研究中应用。众所周知，药物的两个对映异构体可以表现出明显不同的生物学特性。结果，手性小分子的对映选择性合成已成为学术和工业实验室研究的重要领域。最近，镍催化的还原性交叉偶联反应已成为碳碳键形成的直接方法。这些反应通常忍受在轻度条件下发生的一系列官能团，并将廉价的地球金属用作化学计量的还原剂。最重要的是，它们不需要使用预生成的有机金属试剂。为了实现Ni催化还原性交叉偶联反应的全合成潜力，开发这些转换的对映选择性变体至关重要。该提案描述了这一目标的第一个重大进展：开发了四个新的NI催化对映选择性交叉偶联反应。每次转换获得的初步结果为这项研究的可行性提供了令人信服的证据。这项研究将由由PI组成的团队进行，三个化学研究生和一名博士后研究员。作为该项目的一部分，研究生和博士后研究人员将在有机化学的理论，方法和策略中接受严格的培训。这项研究的成功执行将提供新的工具，以使小分子的研究和治疗人类疾病的综合。