Novel Zn(SO2R)2 Salts: Radical-Based Approaches to Functionalized Heteroarenes

新型 Zn(SO2R)2 盐：基于自由基的功能化杂芳烃方法

• 批准号: 8524710
• 负责人: Sarah Elizabeth Wengryniuk
• 金额: $ 4.92万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524710
• 关键词: Alkylation; Attenuated; Biological; CD3 Antigens; Carbon; Chemistry; Communities; Complex; Development; Drug Kinetics; Dyes; Evaluation; Generations; Goals; Human body; Laboratories; Lead; Libraries; Life; Mediating; Medical; Methodology; Methods; Molecular; Nature; Organism; Pesticides; Pharmaceutical Preparations; Polymers; Reagent; Research; Salts; Site; Societies; Vertebral column; Vitamins; alkyl group; appendage; base; biological systems; improved; interest; novel; public health relevance; scaffold; success; tool

DESCRIPTION (provided by applicant): Arenes and heteroarenes are omnipresent in both nature and society, and can be found throughout the human body and in other organisms, as well as in vitamins, drugs, dyes, pesticides, polymers and literally all other aspects of life. As these molecular frameworks form the backbones of some of the most important compounds in both biological systems and industrial applications, the need for methods for their functionalization and derivatization is of the utmost importance. Of particular interest are methods for the direct formation of carbon-carbon bonds through the introduction of alkyl and fluorinated alkyl groups. Alkyl groups serve medicinal chemists by improving pharmacokinetic profiles as well as providing functional handles, and fluoroalkyl appendages are widely utilized as they can serve as attenuated bioisoteres of more reactive and labile functionalities. The proposed research aims to expand upon a recently developed method in our laboratory for the direct, site-selective incorporation of alkyl and fluoroalkyl motifs into heteroarenes. Building on initial proof of concept studies, a "tool kit" of reagents will be synthesized and screened for ther ability to functionalize simple heteroarenes. Once synthesized, a method for sequential addition of multiple groups in a one-pot, site-selective fashion will be developed, taking advantage of the inherent nucleophilic or electrophilic character of each alkyl radical species. Finally, the long-term goal for this research is the application of this novel methodology to complex heteroarene backbones of biologically relevant compounds. Success in these goals would have an immediate impact on the medical community, giving medicinal chemists a new avenue for the rapid generation of interesting and diverse lead compounds for biological evaluation.

描述（由申请人提供）：芳烃和杂芳烃在自然界和社会中无处不在，可以在人体和其他生物体中找到，也可以在维生素、药物、染料、杀虫剂、聚合物和生活的所有其他方面中找到。由于这些分子框架构成了生物系统和工业应用中一些最重要化合物的骨架，因此对它们的功能化和衍生化方法的需求是至关重要的。特别令人感兴趣的是通过引入烷基和氟化烷基直接形成碳-碳键的方法。烷基通过改善药代动力学特征和提供功能柄为药物化学家服务，氟烷基附属物被广泛使用，因为它们可以作为活性更强、功能更不稳定的减毒生物异构体。拟议的研究旨在扩大我们实验室最近开发的一种方法，用于直接，位点选择性地将烷基和氟烷基基序结合到杂环芳烃中。基础上