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: 5211860
• 负责人: ROBERT H HIGGINS
• 金额: --
• 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/5211860
• 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.

本研究项目的重点是阐明其作用机制