Asymmetric Reactions of Oxaziridines

氧氮丙啶的不对称反应

• 批准号: 8247782
• 负责人: TEHSHIK P YOON
• 金额: $ 26.67万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247782
• 关键词: Acids; Alkanes; Alkenes; Amino Acids; Amino Alcohols; Behavior; Biological; Cells; Complex; Copper; Disease; Electrons; Enzymes; Goals; Health; Human; Hydrocarbons; Hydroxylation; Mediating; Metals; Methods; Nitrogen; Organic Chemistry; Oxidants; Oxygen; Pharmaceutical Preparations; Process; Reaction; Reagent; Relative (related person); Research; Salts; Series; Shapes; Specificity; Structure; Sulfides; Techniques; Testing; Titania; Titanium; Transition Elements; Work; base; biological systems; carbene; carbonyl compound; catalyst; chemical synthesis; cycloaddition; design; diene; dioxirane; enolate; fighting; functional group; interest; next generation; nitrone; novel; oxaziridine; oxidation; pathogen; rapid technique; stereochemistry; tool

DESCRIPTION (provided by applicant): Most small, bioactive organic compounds interact specifically with a particular enzyme through a series of oxygen- and nitrogen-containing "functional groups." The specificity and strength of this interaction depends on the overall shape of the molecule and on the arrangement of its functional groups in space (i.e., its "stereochemistry"). The discovery of new compounds with the ability to fight disease or otherwise modulate the behavior of a biological system thus relies on the existence of methods for the synthesis of densely functionalized, well-defined organic molecules. In this regard, a particularly important goal of synthetic organic chemistry is the discovery of new transformations that convert simple, widely available hydrocarbon starting materials into complex, functionalized molecules with high levels of control over their stereochemistry. We are investigating the utility of small, oxygen- and nitrogen-rich compounds called "oxaziridines" in new organic reactions. We hypothesize that (1) transition metal catalysts will increase the reactivity of oxaziridines, (2) fundamentally different reactions will be observed using different catalysts, and (3) these catalysts will have the ability to control the stereochemistry of the resulting value-added products. The proposed research will test these hypotheses in the context of two Specific Aims. First, we will develop copper-catalyzed reactions of oxaziridines for the construction of stereochemically well-defined 1,2- aminoalcohol structures ("aminohydroxylation reactions"). Second, we will develop titanium-catalyzed reactions of oxaziridines for the construction of 1,3-aminoalcohol-containing structures with similarly high levels of stereochemical fidelity ("nitrone cycloadditions"). Successful realization of our project goals will constitute a significant contribution to the field of synthetic organic chemistry and provide a set of powerful tools for the discovery of new drugs, new biological probes, and new materials. PUBLIC HEALTH RELEVANCE: Most drugs are small organic molecules that fight disease by using a series of oxygen- and nitrogen- containing "functional groups" to interact with an enzyme in a pathogen or in a human cell. The ability of a drug to specifically recognize one target enzyme out of thousands and control the progress of a disease depends critically on the overall shape of the molecule and the arrangement of its functional groups in space. We are developing new methods for the rapid, shape-selective construction of well-defined nitrogen- and oxygen-rich molecules, which will enable the discovery and manufacture of the next generation of potent disease-fighting drugs.

描述（由申请人提供）：大多数小型生物活性有机化合物通过一系列含氧和氮的“官能团”与特定酶特异性相互作用。这种相互作用的特异性和强度取决于分子的整体形状及其官能团在空间中的排列（即其“立体化学”）。因此，能够对抗疾病或以其他方式调节生物系统行为的新化合物的发现依赖于合成密集功能化、明确有机分子的方法的存在。在这方面，合成有机化学的一个特别重要的目标是发现新的转化，将简单的、广泛使用的碳氢化合物起始材料转化为复杂的功能化分子，并对其立体化学进行高度控制。我们正在研究称为“氧氮丙啶”的小型富氧和富氮化合物在新有机反应中的用途。我们假设（1）过渡金属催化剂将提高氧氮丙啶的反应性，（2）使用不同的催化剂将观察到根本不同的反应，以及（3）这些催化剂将能够控制所得增值产品的立体化学。拟议的研究将在两个具体目标的背景下测试这些假设。首先，我们将开发氧氮丙啶的铜催化反应，用于构建立体化学明确的 1,2- 氨基醇结构（“氨基羟基化反应”）。其次，我们将开发氧氮丙啶的钛催化反应，用于构建具有类似高水平立体化学保真度的含 1,3-氨基醇结构（“硝酮环加成”）。我们项目目标的成功实现将为有机合成化学领域做出重大贡献，并为新药物、新生物探针和新材料的发现提供一套强大的工具。公共健康相关性：大多数药物都是有机小分子，通过使用一系列含氧和氮的“官能团”与病原体或人体细胞中的酶相互作用来对抗疾病。药物特异性识别数千种靶酶并控制疾病进展的能力关键取决于分子的整体形状及其功能基团在空间中的排列。我们正在开发新方法，用于快速、形状选择性地构建明确的富含氮和氧的分子，这将使下一代有效的抗病药物的发现和制造成为可能。

项目成果

Oxaziridine-mediated intramolecular amination of sp(3)-hybridized C-H bonds.

• DOI: 10.1021/ja906183g
• 发表时间: 2009-09-09
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Allen, Charles P.;Benkovics, Tamas;Turek, Amanda K.;Yoon, Tehshik P.
• 通讯作者: Yoon, Tehshik P.

N-Nosyl Oxaziridines as Terminal Oxidants in Copper(II)-Catalyzed Olefin Oxyaminations.

• DOI: 10.1016/j.tetlet.2010.08.015
• 发表时间: 2010-10-06
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: DePorter, Sandra M.;Jacobsen, Ashley C.;Partridge, Katherine M.;Williamson, Kevin S.;Yoon, Tehshik P.
• 通讯作者: Yoon, Tehshik P.