Asymmetric Synthesis of Nitrogen Heterocycles

氮杂环的不对称合成

• 批准号: 10246858
• 负责人: Tomislav Rovis
• 金额: $ 32万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246858
• 关键词: Alkenes; Amines; Biological; Carbon; Catalysis; Chemicals; Chemistry; Complex; Coupling; Docking; Elements; Eye; Goals; Health; Incidence; Methodology; Methods; Molecular; Nitrogen; Pharmacologic Substance; Positioning Attribute; Prevalence; Pyrrolidines; Reaction; Research; Scaffolding Protein; Source; Streptavidin; Structure; Therapeutic Agents; Time; Transition Elements; Work; catalyst; cycloaddition; design; interest; metalloenzyme; novel; piperidine; programs; scaffold; small molecule; stereochemistry

Project Summary/Abstract Nitrogen is the fourth most common element in pharmaceuticals and biologically active molecules, after only C, H and O. Its incidence greatly eclipses that of other important elements such as S and F. Methods to introduce nitrogen moieties into commonly available starting materials would provide practitioners with rapid access to more complex structures. We have had a long-standing interest in assembling nitrogen heterocycles due to their prevalence and importance. Our work began with approaches to construction of bicyclic structures using cycloaddition chemistry. Over time, it evolved to using C–H activation and generating monocyclic structures. With an eye towards increased utility and impact, we have continued to evolve our approach to using increasingly abundant alkene partners with broadly versatile amine derivatives for the continued synthesis of nitrogen heterocycles as well as acyclic scaffolds. Thus, this competitive renewal is focused on several complementary venues: Aim 1: Stereospecific Catalytic Alkene Difunctionalization Reactions. Alkenes are among the most ubiquitous starting materials available. The delivery of two functionalities across the stereochemically defined alkene allows access to complementary diastereomers if the reaction is stereospecific. We will develop a suite of difunctionalization reactions including carboamination, carbocarbation and related transformations. Where possible we will use unfunctionalized precursors in such a way to increase utility and ease of execution. Aim 2: Chemoselective Coupling of Alkenes and Nitrogen Electrophiles. We will extend alkene functionalization chemistry to convert simple -olefins directly into pyrrolidines, piperidines and allylic amine derivatives, functionalizing not just the alkene itself but also the allylic, homoallylic and bis-homoallylic positions. Aim 3: Design of Artificial Metalloenzymes for Enhanced Reactivity and Asymmetric Catalysis. Many of these reactions create chiral products. We will control the absolute stereochemistry of the transformations with novel metalloenzymes derived from transition metal catalysts docked within monomeric streptavidin protein scaffolds.

项目摘要/摘要 氮是药物和生物活性分子中的第四大元素，之后 只有C，H和O。它的事件极大地黯然失色。 将氮部分引入常用的原材料将为从业者提供快速 访问更复杂的结构。我们对组装氮杂环有很长的兴趣 由于它们的流行和重要性。我们的工作始于生物结构的建设方法 使用环加成化学。随着时间的流逝，它演变为使用C – H激活和产生单核细胞 结构。着眼于提高效用和影响，我们继续发展我们的方法 使用越来越丰富的烯烃合作伙伴具有广泛的胺衍生物 氮杂环和无环支架的合成。那是这种竞争性更新的重点 几个完整的场所： 目标1：立体催化烯烃扩散反应。烯烃是最普遍的 起始材料可用。在立体化学定义的烯烃中传递两个功能 如果反应是立体特异性的，则允许访问可以完成非对映异构体。我们将开发一套 连接性反应，包括碳水化合物，碳碳和相关转换。在哪里 我们可能会以这种方式使用不官能化的前体来提高效用和易于执行。 AIM 2：烷烃和氮电矿的化学选择性偶联。我们将扩展烯烃功能化 化学反应将简单的-烯烃直接转化为吡咯烷，哌啶和种植胺衍生物， 不仅使烯烃本身，还可以使烯丙基，同型和双旋转的位置官能化。 AIM 3：设计人工金属酶，以增强反应性和不对称催化。其中许多 反应会产生手性产品。我们将通过新颖的方式控制转换的绝对立体化学 源自单体链霉亲和素蛋白支架内的过渡金属催化剂的金属酶。