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）：一般有效的化学反应的开发为生物学和药物上重要的分子的设计和合成提供了必要的工具。由于对映体异构体经常表现出不同的生物学活性，因此越来越强调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，使用对映体纯化合物的使用可改善所需的活性并降低毒性，除其他临床益处外。因此，食品和药物管理局要求对两种新手性药物的对映异构体进行评估，然后才能提交批准。在制备手性非流行分子的不同方法中，基于过渡金属的非对称催化为发展具有成本效益和环境良性方法的发展提供了希望。在当今的制药行业中，单一对映体手性药物的市场份额不断上升，对新的强大立体选择性催化过程的需求越来越大。通过硝基插入的催化C-H胺化代表了最重要的化学转化类别之一。这种类型的催化硝酸盐转移过程为通过立体选择C-N键形成在丰富的烃中的C-H键在功能上提供了直接和一般的方法。它是设计和合成生物学和药物上重要的手性胺分子的宝贵工具。该研究项目用于开发用于立体选择C-H胺化反应的新催化系统。对于这一特定建议，我们将重点介绍钴（II）手性卟啉复合物[CO（ii）（POR*）]作为一类新的手性催化剂，以推动对映选择性的C-H氨基化反应，以促进对含量糖尿病和氨基含量的有价值的合成的立体选择。这些新的催化方法将应用于生物学和药物有趣的含氮分子的立体选择性合成，包括光学活性氨基酸，二氨基酸，二氨基和氟化氨基酸的化合物，这些化合物是抗生素或TAMOR成像剂。我们希望这些研究最终将导致用于一般C-H氨基反应的实用CO（II）催化系统的开发，这些催化系统可以成功应用于生物学上重要的天然产物和药品有趣的小分子的立体选择性合成。