Catalytic Asymmetric Oxidation of Alkenes and Alkanes

烯烃和烷烃的催化不对称氧化

• 批准号: 10356054
• 负责人: DUY H HUA
• 金额: $ 29.95万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356054
• 关键词: Acetamides; Acetates; Acids; Alkanes; Alkenes; Alzheimer' s Disease; Amines; Amino Acids; Aptitude; Atmosphere; Biological; Carbon; Chemicals; Chemistry; Circular Dichroism; Complement; Complex; Copper; Cyclization; Cyclohexanes; Cycloparaffins; Data; Diamide; Distal; Economics; Erythro; Esters; Estrone; Generations; Goals; Gold; Hydrogen; Hydrogen Bonding; Hydrogen Peroxide; Hydroxyl Radical; Image; Imines; Imprisonment; Investigation; Ketones; Knowledge; Lactams; Lactones; Light; Malignant Neoplasms; Metals; Methodology; Methods; Molecular Conformation; Natural Product Drug; Nitrogen; Optics; Oxidants; Oxides; Oxygen; Palladium; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Polymers; Property; Pyrrolidinones; Reaction; Reporting; Research Project Grants; Ribose; Site; Vertebral column; Water; base; bioactive natural products; carbene; catalyst; chiral molecule; design; diene; dimer; functional group; hydrophilicity; improved; interest; metal oxide; nanoGold; nanocluster; nanoparticle; nanoscale; oxidation; particle; stereochemistry

Project Summary The discovery of new methodologies to advance the fields of synthetic organic, medicinal, and material chemistry is critical in the synthesis of pharmaceuticals. Particularly, catalytic asymmetric oxidation reactions are economic, since only a small amount of the catalyst is needed. The oxidation reactions provide chiral molecules and additional functionalities onto the molecules for functional group manipulation. Recently, we discovered a new class of polymers, namely chiral-substituted poly-N-vinylpyrrolidinones (CSPVPs), for stabilization of bimetallic nanoclusters such as palladium/gold or copper/gold nanoparticles in the induction of chirality. These chiral polymers wrap around (or incarcerate) the nanometer-sized (~3 nm) bimetallic nanoparticles and catalyze a number of enantioselective oxidation reactions using oxygen or hydrogen peroxide as the oxidant. For example, alkenes were oxidized by 0.5 mol% of Pd/Au (3:1)-chiral polymer 2R under 2 atmospheric of oxygen in water to give the syn-dihydroxylated products in 73 – 86% chemical and 97 - 99% ee optical yields. Various cycloalkanes underwent regio- and enantio-selective C-H oxidation with 5 mol% Cu/Au (3:1)-2R and 30% hydrogen peroxide to produce the corresponding chiral oxo-molecules in very good chemical and excellent optical yields. We further discovered enantioselective desymmetrization of -dialkenyl-alkanols and -dialkenyl–amino acid ethyl esters with 4 mol% Cu/Au-2R and hydrogen peroxide to give chiral disubstituted lactones and lactams, respectively, in 91 – 96% ee. A number of medium-sized natural products and drugs including N- acetylamantadine, oxymetrine, ambroxide, and 3-pivaloyl estrone were also oxidized regioselectively to give the corresponding mono-oxygenated products in good yields. These exciting results prompted us to propose studies of the scope and mechanisms of the catalytic asymmetric oxidation reactions and late-stage aliphatic C-H oxidation of bioactive complex molecules. Our goal is to discover useful synthetic methodologies in catalytic asymmetric synthesis. Three specific aims are designed to achieve our goal: (1) optimization of the CSPVPs and studies of the scope, mechanisms, and regio- and enantio-selectivity in the oxidation of alkenes and alkanes; (2) investigation of the catalytic asymmetric ring closing reactions by forming C-O and C-N bond from dienols and diene amines, respectively, and the asymmetric imine-Heck C-C bond forming reaction; and (3) investigation of the predictive regioselectivity of C-H oxidation of bioactive complex molecules, which may alter or improve the pharmacological and biological properties of the molecules.

项目概要 发现新方法来推进合成有机、药物和材料化学领域的发展 特别是催化不对称氧化反应是经济的， 因为只需要少量的催化剂，氧化反应提供手性分子并且 最近，我们发现了一种新的功能。 一类聚合物，即手性取代的聚-N-乙烯基吡咯烷酮 (CSPVP)，用于稳定双金属 纳米团簇，例如钯/金或铜/金纳米粒子，可诱导手性。 聚合物包裹（或嵌入）纳米尺寸（~3 nm）双金属纳米颗粒并催化 使用氧气或过氧化氢作为氧化剂的对映选择性氧化反应的数量。 在2个大气压的水中，0.5 mol%的Pd/Au (3:1)-手性聚合物2R将烯烃氧化为 得到各种环烷烃的化学产率 73 – 86% 和 ee 光学产率 97 – 99% 的顺式二羟基化产物。 使用 5 mol% Cu/Au (3:1)-2R 和 30% 过氧化氢进行区域选择性和对映选择性 C-H 氧化 我们进一步以非常好的化学产率和优异的光学产率生产相应的手性含氧分子。 发现 α-二烯基-烷醇和 -二烯基-氨基酸乙基的对映选择性去对称化 与 4 mol% Cu/Au-2R 和过氧化氢形成酯，得到手性二取代内酯和内酰胺， 分别为 91 – 96% ee 的多种中型天然产物和药物，包括 N- 乙酰金刚烷胺、氧米曲林、氨溴索和 3-新戊酰雌酮也被区域选择性氧化，得到 相应的单氧化产物具有良好的产率。这些令人兴奋的结果促使我们提出研究建议。 催化不对称氧化反应和后期脂肪族C-H的范围和机制 我们的目标是发现催化中有用的合成方法。 不对称合成设计了三个具体目标来实现我们的目标：（1）CSPVP 的优化。 以及烯烃和烷烃氧化的范围、机制以及区域和对映选择性的研究； (2)二烯醇形成C-O和C-N键催化不对称闭环反应的研究 和二烯胺，以及不对称亚胺-Heck C-C键形成反应和（3）研究； 生物活性复合物分子 C-H 氧化的预测区域选择性，这可能会改变或改善 分子的药理学和生物学特性。

项目成果

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes.

研究 HCAR2 拮抗剂作为调节牛白细胞的潜在策略。

• DOI: 10.1186/s40104-024-00999-5
• 发表时间: 2024
• 期刊: Journal of animal science and biotechnology
• 影响因子: 7
• 作者: Mamedova,LamanK;Krogstad,KirbyC;McDonald,PaitonO;Pokhrel,Laxman;Hua,DuyH;Titgemeyer,EvanC;Bradford,BarryJ
• 通讯作者: Bradford,BarryJ

Synthesis of Chiral Tricyclic Pyrone Molecules via Palladium(0)-Catalyzed Displacement Reactions of Chiral Tricyclic Pyrone Acetate With Azide or Amine.

通过钯(0)催化手性三环吡喃酮乙酸酯与叠氮化物或胺的置换反应合成手性三环吡喃酮分子。

• DOI: 10.1002/slct.202301435
• 发表时间: 2023
• 期刊: ChemistrySelect
• 影响因子: 2.1
• 作者: Morita,Shunya;Ren,Zhaoyang;Fan,Huafang;Hua,DuyH
• 通讯作者: Hua,DuyH

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids

• DOI: 10.15698/mic2020.06.719
• 发表时间: 2020-06-01
• 期刊: MICROBIAL CELL
• 影响因子: 4.6
• 作者: Edouarzin, Edruce;Horn, Connor;Vediyappan, Govindsamy
• 通讯作者: Vediyappan, Govindsamy

Comparison of strategies for enhancing RNA interference efficiency in Ostrinia nubilalis.

增强玉米螟 RNA 干扰效率的策略比较。

• DOI: 10.1002/ps.6114
• 发表时间: 2021-03
• 期刊: Pest management science
• 影响因子: 4.1
• 作者: Cooper AM;Song H;Yu Z;Biondi M;Bai J;Shi X;Ren Z;Weerasekara SM;Hua DH;Silver K;Zhang J;Zhu KY
• 通讯作者: Zhu KY