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，并且可以在整个人体和其他生物体中以及维生素、药物、染料、杀虫剂、聚合物和几乎所有其他生活方面中发现。由于这些分子框架形成生物系统和工业应用中一些最重要的化合物的骨架，因此对它们的官能化和衍生化方法的需求是极其重要的。特别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。烷基基团通过改善药代动力学特征以及提供功能性手柄而为药物化学家服务，并且氟烷基附属物被广泛使用，因为它们可以用作更具反应性和不稳定官能团的衰减生物等排体。拟议的研究旨在扩大后，在我们的实验室最近开发的方法，直接，位点选择性纳入烷基和氟烷基基序到杂芳烃。基础上 在初步的概念验证研究中，将合成一种试剂“工具包”，并筛选其功能化简单杂芳烃的能力。一旦合成，将开发以一锅法、位点选择性方式顺序添加多个基团的方法，利用每个烷基自由基物种的固有亲核或亲电特性。最后，本研究的长期目标是将这种新方法应用于生物相关化合物的杂芳烃骨架的复杂化。这些目标的成功将对医学界产生直接影响，为药物化学家提供了一条新的途径，可以快速生成有趣且多样化的先导化合物，用于生物学评价。