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.

项目摘要 发现新方法可以推进合成有机，医学和材料化学领域 对于药物的合成至关重要。特别是，催化不对称氧化反应是经济的， 由于仅需要少量催化剂。氧化反应提供手性分子和 在分子上进行功能组操作的其他功能。最近，我们发现了一个新的 聚合物类别，即手性阳性二乙烯基吡啶酮（CSPVPS），用于稳定双金属 纳米簇（例如钯/金或铜/金纳米颗粒）在诱导手性方面。这些手性 聚合物在纳米尺寸（〜3 nm）双金属纳米颗粒周围（或监禁）缠绕并催化A 使用氧或过氧化氢作为氧化物的对映选择性氧化反应的数量。例如， 将烷烃用Pd/au的0.5 mol％（3：1）的0.5摩尔％（3：1） - 在水中的2个氧气大气下氧化 给出73 - 86％化学物质和97 - 99％EE光学产量的同步二羟基化产物。各种环烷烃 用5 mol％Cu/au（3：1）-2R和30％过氧化氢进行了区域和对映选择性C-H氧化 以非常好的化学和出色的光学产量产生相应的手性氧摩尔分子。我们进一步 发现了dialkenyl-烷醇和-二氨基 - 氨基酸乙基的对映选择性的对称性对称性 具有4 mol％Cu/au-2r和过氧化氢的酯提供手性脱取代的内酯和乳糖， 分别在91 - 96％的EE中。许多中型天然产品和包括N-的药物 乙酰基胺，氧合，腹氧化物和3-鸟酰雌酮也被氧化以调节以得到 相应的单氧产品的产量良好。这些令人兴奋的结果促使我们提出了研究 催化不对称氧化反应的范围和机制和晚期脂肪族C-H 生物活性复合物分子的氧化。我们的目标是在催化中发现有用的合成方法 不对称合成。旨在实现我们的目标的三个特定目标：（1）优化CSPVPS 以及烯烃和烷烃氧化中的范围，机制以及区域和对映体选择性的研究； （2）通过形成二烯的C-O和C-N键来研究催化不对称环闭合反应 分别是二烯胺，以及不对称的亚胺-HECK C-C键形成反应； （3）调查 生物活性复合物分子的C-H氧化物的预测调节选择性，这可能会改变或改善 分子的药理和生物学特性。

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