New Catalytic Systems for Stereoselective C-H Amination

用于立体选择性 C-H 胺化的新型催化系统

• 批准号: 9188930
• 负责人: X. Peter ZHANG
• 金额: $ 15.38万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9188930
• 关键词: New; Catalytic; Systems; Stereoselective; Amination

DESCRIPTION (provided by applicant): The development of general and efficient chemical reactions provides the necessary tools for the design and synthesis of biologically and pharmaceutically important molecules. There has been a growing emphasis on developing practical methodologies for the synthesis of enantiomerically pure compounds, since enantiomeric isomers often exhibit different biological activities. Compared to a racemic mixture, the use of an enantiomerically pure compound improves the desired activity and reduces toxicity in addition to other clinical benefits. Consequently, the Food and Drug Administration requires the evaluation of both enantiomers of new chiral drugs before they can be submitted for approval. Among different approaches for preparing chiral non-racemic molecules, transition metal-based asymmetric catalysis offers promise for the development of cost-effective and environmentally benign methods. In today's pharmaceutical industry, where the market share of single enantiomer chiral drugs continues to rise, there are growing demands for new powerful stereoselective catalytic processes. Catalytic C-H amination via nitrene insertion represents one of the most important classes of chemical transformations. This type of catalytic nitrene transfer process provides a direct and general approach for the functionalization of C-H bonds in abundant hydrocarbons through stereoselective C-N bond formation. It serves as a valuable tool for the design and synthesis of biologically and pharmaceutically important chiral amine molecules. This research project is directed toward the development of new catalytic systems for stereoselective C-H amination reactions. For this particular proposal, we will focus on the utilization of cobalt(II) chiral porphyrin complexes [Co(II)(Por*)] as a class of new chiral catalyts to advance the enantioselective C-H amination reactions for stereoselective synthesis of valuable diamines and amino alcohols. These new catalytic methods will be applied to the stereoselective synthesis of biologically and pharmaceutically interesting nitrogen-containing molecules, including optically active amino acid-, diamino acid-, and fluoridated amino acid-based compounds that are antibiotics or tumor imaging agents. We hope these studies will ultimately lead to the development of practical Co(II)-based catalytic systems for general C-H amination reactions that can be successfully applied toward the stereoselective synthesis of biologically important natural products and pharmaceutically interesting small molecules.

描述(由申请人提供)：普通和有效的化学反应的发展为设计和合成具有生物和药学意义的重要分子提供了必要的工具。由于对映异构体往往表现出不同的生物活性，人们越来越重视开发合成对映体纯化合物的实用方法。与外消旋混合物相比，使用对映体纯的化合物可以提高预期的活性并降低毒性，此外还有其他临床好处。因此，食品和药物管理局要求对新手性药物的两种对映体进行评估，然后才能提交审批。在制备手性非外消旋分子的不同方法中，基于过渡金属的不对称催化为开发低成本和环境友好的方法提供了希望。在今天的制药工业中，单一对映体手性药物的市场份额持续上升，对新的强大的立体选择性催化工艺的需求越来越大。硝基插入催化C-H胺化反应是最重要的一类化学转化反应。这种催化的硝基转移过程为碳氢键的立体选择性生成提供了一种直接的、通用的方法。它是设计和合成具有生物和药学意义的重要手性胺分子的宝贵工具。本研究项目旨在开发立体选择性C-H胺化反应的新催化体系。对于这一特殊的建议，我们将重点利用钴(II)手性卟啉配合物[Co(II)(Por*)]作为一类新型手性催化剂来推进用于立体选择性合成有价值的二胺和氨基醇的不对称C-H胺化反应。这些新的催化方法将应用于立体选择性地合成具有生物和药用价值的含氮分子，包括光学活性氨基酸、二氨基酸和含氟氨基酸类化合物，如抗生素或肿瘤显像剂。我们希望这些研究将最终导致开发实用的基于Co(II)的催化体系，用于一般的C-H胺化反应，从而成功地应用于具有重要生物意义的天然产物和具有药用价值的小分子的立体选择性合成。