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: 8635372
• 负责人: X. Peter ZHANG
• 金额: $ 21.73万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 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/8635372
• 关键词: Acids; Address; Amination; Amines; Amino Acids; Amino Alcohols; Antibiotics; Azides; Benign; Biological; Biological Factors; Catalysis; Chemicals; Clinical; Cobalt; Complex; Development; Diamines; Diamino Amino Acids; Drug Industry; Electrons; Evaluation; Exhibits; Fluorine; Gases; Goals; Hydrocarbons; Hydrogen Bonding; Image; Isomerism; Lead; Ligands; Marketing; Metals; Methodology; Methods; Nature; Nitrogen; Oxidants; Pharmaceutical Preparations; Porphyrins; Process; Reaction; Reagent; Research; Research Project Grants; Source; Stress; System; Toxic effect; Transition Elements; United States Food and Drug Administration; base; carboxylate; catalyst; chemical reaction; cost effective; design; direct application; enantiomer; improved; interest; nitrene; public health relevance; small molecule; tool; tumor

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）：通用和有效化学反应的发展为设计和合成生物学和药学上重要的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，因此开发合成对映异构体纯化合物的实用方法越来越受到重视。与外消旋混合物相比，使用对映体纯的化合物除了其他临床益处之外还提高了所需的活性并降低了毒性。因此，食品和药物管理局要求在新的手性药物提交批准之前对其两种对映体进行评估。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具有成本效益和环境友好的方法提供了希望。在当今的制药工业中，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方法的需求不断增长。通过氮烯插入的催化C-H胺化是最重要的化学转化类型之一。这类催化氮烯转移过程为通过立体选择性C-N键形成使丰富烃中的C-H键官能化提供了直接和通用的方法。它是设计和合成生物学和药学上重要的手性胺分子的有价值的工具。本研究计划旨在发展立体选择性C-H胺化反应的新型催化体系。对于这个特殊的建议，我们将集中在利用钴（II）的手性卟啉配合物[Co（II）（Por*）]作为一类新的手性催化剂，以推进对映选择性的C-H胺化反应的立体选择性合成有价值的二胺和氨基醇。这些新的催化方法将被应用于立体选择性合成生物学和药学上有趣的含氮分子，包括光学活性的氨基酸，二氨基酸，和氟化的氨基酸为基础的化合物，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Co（II）为基础的催化体系，一般的C-H胺化反应，可以成功地应用于生物学上重要的天然产物和药学上有趣的小分子的立体选择性合成。