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: 8642534
• 负责人: Sarah Elizabeth Wengryniuk
• 金额: $ 4.17万
• 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 2014-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642534
• 关键词: Adverse effects; Alkylation; Area; Attenuated; Biological; Carbon; Cellular Assay; Chemistry; Communities; Complex; Development; Drug Kinetics; Dyes; Electronics; Evaluation; Generations; Goals; Hand; Human body; Hydrogen Bonding; Laboratories; Lead; Libraries; Life; Mediating; Medical; Methodology; Methods; Molecular; Mono-S; Nature; Organism; Parents; Pesticides; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Polymers; Property; Reagent; Research; Salts; Site; Societies; Vertebral column; Vitamins; Zinc; alkyl group; appendage; base; biological systems; design; functional group; improved; interest; novel; programs; scaffold; screening; 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(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找到。由于这些分子骨架构成了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至关重要的。特别感兴趣的是通过引入烷基和氟烷基直接形成碳-碳键的方法。烷基通过改善药代动力学曲线和提供功能手柄为药物化学家服务，而氟烷基附件由于可以作为更具活性和不稳定官能团的弱化生物异构体而被广泛使用。这项拟议的研究旨在扩展我们实验室最近开发的一种方法，用于将烷基和氟烷基基元直接、选择性地结合到杂芳烃中。在基础上建设 概念研究的初步证明，将合成试剂的“工具包”，并筛选其使简单杂芳烃功能化的能力。一旦合成，将利用每个烷基物种固有的亲核或亲电特性，开发一种一锅法、位置选择性地顺序加成多个基团的方法。最后，这项研究的长期目标是将这一新方法应用于生物相关化合物的复杂杂芳烃骨架。这些目标的成功将对医学界产生立竿见影的影响，为药物化学家提供一条快速产生有趣和多样化的先导化合物进行生物评估的新途径。

项目成果

Regioselective bromination of fused heterocyclic N-oxides.

• DOI: 10.1021/ol3034675
• 发表时间: 2013-01
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Sarah E. Wengryniuk;A. Weickgenannt;Christopher A. Reiher;N. Strotman;K. Chen;Martin D. Eastgate;P. Baran