Catalytic Asymmetric Oxidation: Easy Entry to Highly Functionalized Molecules

催化不对称氧化：轻松进入高功能化分子

基本信息

批准号：
7666017
负责人：
HISASHI None YAMAMOTO
金额：
$ 33.06万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7666017
关键词：
3-hydroxybutanal Academia Acids Alcohols Alder plant Area Attention Carbon Catalysis Chemistry Complex Data Development Diels Alder reaction Drug Industry Employment Ethers Future Goals Grant Growth Halogens Health Care Costs Human Industry Kinetics Knowledge Laboratories Libraries Ligands Methodology Methods Molecular Nitrogen Nitroso Compounds Organic Synthesis Outcome Oxygen Pharmaceutical Chemistry Pharmaceutical Preparations Process Production Protocols documentation Public Health Reaction Reagent Research Research Personnel Resolution Sales Science Social Welfare Societies Solutions Sulfur System Technology Testing Training United States National Institutes of Health Vanadium career catalyst chiral molecule cycloaddition design drug development enol experience functional group graduate student halogenation innovation novel oxidation programs pyridine success tool trend wasting

项目摘要

DESCRIPTION (provided by applicant): Project summary: Modern drugs are highly functionalized molecules, and often these molecules are chiral. The most promising solution for production of these molecules has relied on an asymmetric catalytic process, especially catalytic asymmetric oxidation, which can introduce multi functional groups into the molecule. The long-term goal is to develop catalytic asymmetric oxidation processes which can create highly functionalized drugs at a useful level of selectivity and scalability. The objective of developing these catalysts is to provide reliable and easy access to make molecules previously unattainable in a simple manner. The key to success is proper molecular design of an oxidation catalyst. Catalytic selective oxidation can introduce oxygen, nitrogen, and halogen to the substrate catalytically and selectively. Guided by strong preliminary data, this hypothesis will be tested by pursuing four specific aims: 1) asymmetric construction of quaternary carbon using nitroso chemistry, 2) development of catalytic asymmetric nitroso hetero-Diels-Alder and related asymmetric cycloadditions, 3) asymmetric epoxidation and its kinetic resolution, and 4) asymmetric halogenation. All four approaches are innovative, because each of them is an unknown process which capitalizes on a totally new concept of catalyst design developed by our group using earlier NIH support. They also take advantage of a number of ligand libraries which are available in no other laboratory. The proposed research is significant, because it is expected to provide a fine toolbox of catalysts, which will make possible the provision of previously unattainable complex molecules needed to develop entirely new pharmacologic strategies in the future. Relevance to Public Health: This is an important area of organic synthesis that has potential applicability to efficiently strengthen drugs, ultimately including those for human beings. Finally, the projects described herein will provide excellent training for graduate students and postdoctoral associates in catalysis, experience that will prepare them well for independent research careers to contribute for public health.

描述（由申请人提供）：项目摘要：现代药物是高度功能化的分子，通常这些分子是手性的。产生这些分子的最有希望的解决方案依赖于不对称的催化过程，尤其是催化不对称氧化，可以将多官能基团引入分子中。长期目标是开发催化不对称的氧化过程，这些过程可以在有用的选择性和可伸缩性水平上产生高度功能化的药物。开发这些催化剂的目的是提供可靠且易于访问，以使以前无法实现的分子以简单的方式提供。成功的关键是氧化催化剂的正确分子设计。催化选择性氧化可以通过催化和有选择地将氧，氮和卤素引入氧气，氮和卤素。在强大的初步数据的指导下，将通过追求四个具体目的来检验该假设：1）使用硝基化学的非对称季碳构建，2）开发催化催化不对称的硝基氧化物杂型氧化甲烷 - 氧气及相关的不对称环量，3）不对称的孔源和4）kinecentric和4）kincentic和4）kincentic and kinection和4）。所有四种方法都是创新的，因为它们都是一个未知的过程，它利用了我们小组使用早期NIH支持开发的全新的催化剂设计概念。他们还利用了许多其他实验室中可用的配体库。拟议的研究非常重要，因为预计它将提供催化剂的精细工具箱，这将使未来开发全新的药理学策略所需的先前无法实现的复杂分子提供。与公共卫生相关：这是有机综合的重要领域，具有有效加强药物的潜在适用性，最终包括人类的药物。最后，本文所述的项目将为催化研究生和博士后伙伴提供出色的培训，这些经验将为独立研究生涯做好准备，为公共卫生做出贡献。