Regio- and enantioselective electrophilic aromatic substitution on drug-like molecules

药物样分子上的区域和对映选择性亲电子芳香取代

• 批准号: 1664565
• 负责人: Jeffrey Gustafson
• 金额: $ 39万
• 依托单位: San Diego State University Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1664565&HistoricalAwards=false
• 关键词: Regio; enantioselective; electrophilic; aromatic; substitution

The Chemical Catalysis Program of the Chemistry Division supports the project by Professor Gustafson. Professor Gustafson is a faculty member in the Department of Chemistry at San Diego State University. He is developing new classes of catalysts for electrophilic aromatic substitution. The goal of this research program is to design new catalysts that allow for the direct functionalization of both simple and complex aromatic molecules, including pharmaceuticals and proteins. Lewis basic groups are capable of activating electrophiles and are readily incorporated into catalyst structures, allowing for modular catalyst design. The project lies at the interface of catalytic, synthetic and physical organic chemistry. Therefore, it is well suited for the education of scientists at all levels. Professor Gustafson's group is well positioned to provide the highest level of education and training for students underrepresented in science due to San Diego State University's unique and diverse student population. Outreach activities involving underrepresented students at community colleges are part of the project. Lewis bases can catalytically activate diverse electrophiles towards electrophilic addition reactions. The Gustafson group has recently demonstrated that Lewis bases such as thioureas and phosphine sulfides can catalyze the halogenation or sulfenylation of aromatic feedstocks under very mild conditions. Preliminary mechanistic studies suggest this chemistry proceeds through a covalent halenium-catalyst adduct, and that the structure of the catalyst can influence the reaction outcome. The proposed research involves both in-depth mechanistic studies and the development of new catalysts to extend the project to more complex systems. There are three major questions this proposal strives to answer: How do Lewis base catalysts control the regioselectivity of phenol chlorination, and can this selectivity be extended to other classes of arenes? Second, how do Lewis bases conjugated to Bronsted acids catalyze the mild sulfenylation of heterocycles, and can this reaction be extended to peptides, proteins, and natural products? Furthermore, can changes in the Lewis base lead to chemoselectivity towards other classes of arenes? Finally, can chiral Lewis base catalysts be designed to effect enantioselective halogenation and sulfenylation? The educational plan includes outreach to underrepresented students at local community colleges to introduce them to research opportunities available to undergraduates. This outreach activity includes hands-on presentations at local community colleges that introduce students to computational chemistry in the context of the conformational analysis of butane.

化学系的化学催化计划支持古斯塔夫森教授的项目。古斯塔夫森教授是圣地亚哥州立大学化学系的教员。 他正在开发新型的芳香族亲电取代催化剂。 该研究计划的目标是设计新的催化剂，使简单和复杂的芳香分子，包括药物和蛋白质的直接官能化。刘易斯碱性基团能够活化亲电体，并且容易结合到催化剂结构中，从而允许模块化催化剂设计。 该项目位于催化，合成和物理有机化学的界面。因此，它非常适合各级科学家的教育。 古斯塔夫森教授的小组处于有利地位，为学生提供教育和培训的最高水平，在科学由于圣地亚哥州立大学的独特和多样化的学生群体的代表性不足。 该项目的一部分内容是，在社区学院开展涉及代表性不足的学生的外联活动。刘易斯碱可以催化活化多种亲电试剂进行亲电加成反应。Gustafson小组最近证明刘易斯碱如硫脲和硫化膦可以在非常温和的条件下催化芳族原料的卤化或亚磺酰化。初步的机理研究表明，这种化学反应是通过共价卤素催化剂加合物进行的，催化剂的结构会影响反应结果。 拟议的研究涉及深入的机理研究和新催化剂的开发，以将该项目扩展到更复杂的系统。 有三个主要的问题，这个建议努力回答：刘易斯碱催化剂如何控制苯酚氯化的区域选择性，这种选择性可以扩展到其他类别的芳烃？第二，与布朗斯台德酸共轭的刘易斯碱如何催化杂环的温和磺酰化，该反应能否扩展到肽、蛋白质和天然产物？此外，刘易斯碱的变化是否会导致对其他类别芳烃的化学选择性？ 最后，能否设计手性刘易斯碱催化剂来实现对映选择性卤化和亚磺酰化？教育计划包括向当地社区学院代表性不足的学生进行宣传，向他们介绍本科生可以获得的研究机会。这项推广活动包括在当地社区学院的动手演示，向学生介绍丁烷构象分析背景下的计算化学。

项目成果

Photocatalytic Oxidative C–H Thiolation: Synthesis of Benzothiazoles and Sulfenylated Indoles

光催化氧化 C–H 硫醇化：苯并噻唑和磺化吲哚的合成

• DOI: 10.1055/s-0039-1690107
• 发表时间: 2019
• 期刊: Synlett
• 影响因子: 2
• 作者: Dinh, Andrew N.;Nguyen, Ashley D.;Aceves, Ernesto Millan;Albright, Samuel T.;Cedano, Mario R.;Smith, Diane K.;Gustafson, Jeffrey L.
• 通讯作者: Gustafson, Jeffrey L.