MECHANISM OF RING OPENING OF AZETIDINES AND AZETIDINE-3-OLS

氮杂环丁烷和氮杂环丁烷-3-OLS的开环机理

• 批准号: 3734535
• 负责人: ROBERT H HIGGINS
• 金额: --
• 依托单位: FAYETTEVILLE STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3734535
• 关键词: angina pectoris; antiarrhythmic agent; antihypertensive agents; beta antiadrenergic agent; carbon; chemical structure function; chemical substitution; conformation; deuterium; drug design /synthesis /production; heart disorder chemotherapy; high performance liquid chromatography; hypertension; molecular shape; nitrogenous heterocyclic compound; nuclear magnetic resonance spectroscopy; stable isotope

The focus of this research project is to elucidate the mechanism of the ring-opening of the azetidine ring. The reactions that will be undertaken will involve the action of a series of meta- and para- substituted phenols on 1-alkylazetidines rand 1-alkyl-2-methylazetidines. The reaction products will be separated and isolated by fractional distillation and high performance liquid chromatography. Characterization of these reaction products will be made by IR, 1H and 13C NMR spectral studies. A second dimension of the project will involve kinetic studies of the ring- opening reactions by a suitable combination of spectral studies. During the previous funding period, research-size quantities of compounds possessing beta-adrenolytic properties (helpful in controlling hypertension, angina pectoris and cardiac arrhythmia) have been prepared by our laboratory using these reactions. During the proposed funding period this project will be aimed at providing a detailed understanding of the mechanism, with the ultimate objective of providing not only a convenient means of preparing new compounds but also new classes of compounds possessing more specificity for the treatment of the organs affected by these diseases--the heart and the blood vessels. The research design will involve: (1) the synthesis of N-substituted azetidines by various methods; (2) isolation of the products by distillation and/or various chromatographic techniques; (3) ring-opening of N-substituted azetidines with substituted phenols; (4) separation, isolation and characterization of the ring opening products; and (5) kinetic studies of the ring opening reactions. Students will participate in every aspect of this project, including preparation of starting materials, performing kinetics, interpreting data from IR and NMR spectra, etc.

本课题的研究重点是阐明心绞痛的发病机制。 氮杂环的开环。将会采取的反应 将涉及一系列间位和对位取代苯酚的作用 1-烷基-2-甲基氮杂环丁烷和1-烷基-2-甲基氮杂环丁烷。他们的反应 产品将通过分馏和分离来分离和分离 高效液相色谱仪。对这些的描述 反应产物将通过IR、1H和13C核磁共振波谱研究得到。一个 该项目的第二个维度将涉及对光环的动力学研究- 通过适当的光谱研究结合开环反应。 在之前的资助期间，研究规模的化合物数量 具有β-肾上腺素分解特性(有助于控制 高血压、心绞痛和心律失常)已经准备好 由我们的实验室使用这些反应。在提议的资助期间 在此期间，本项目的目的是提供对 该机制的最终目标是不仅提供一个 制备新化合物的方便手段，也是新类别的 对器官治疗更具特异性的化合物 受这些疾病的影响--心脏和血管。这项研究 设计将涉及：(1)N-取代氮杂环丁烷的合成 各种方法；(2)通过蒸馏和/或蒸馏分离产品 各种层析技术；(3)N-取代的开环 含取代酚的氮杂环丁烷；(4)分离、分离和 开环产物的表征；(5)开环反应动力学研究 开环反应。 学生将参与这个项目的方方面面，包括 起始材料的准备，执行动力学，解释数据 从红外光谱和核磁共振光谱等方面进行了分析。