New Methods for Heterocycle Synthesis

杂环合成新方法

• 批准号: 1956328
• 负责人: Carl Lovely
• 金额: $ 38.4万
• 依托单位: University of Texas at Arlington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1956328&HistoricalAwards=false
• 关键词: New; Methods; Heterocycle; Synthesis

With this Award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Carl Lovely, University of Texas-Arlington to work with undergraduate and graduate students to develop new methods for the construction of complex organic structures, such as those that might used in chemical biology or medicinal chemistry studies. In the present research, new methods and strategies are being invented to allow the assembly of complex molecular frameworks through tandem reactions in order to increase synthetic efficiency. Tandem reactions involve the sequencing of two or more chemical reactions such that the first reaction sets up the second and so on. Such strategies have potential to increase efficiency by reducing the number of synthetic steps required in a process, thereby reducing the use of organic solvent and the number of purification steps required. Plans are outlined to apply the new methodology to the synthesis of two natural products originally isolated from marine invertebrates. These natural products are of interest due to their unusual bicyclic architectures. These challenging target structures have both inspired the methodology and are seen to have potential for chemical biology studies Additional benefits which accrue from this project include the recruitment and participation of under-represented high school, undergraduate and graduate students. In particular, one project has been specifically designed with the participation of high school students in mind. In this latter context, students have the opportunity to do research in organic synthesis that otherwise would not be available to them.Professor Lovely and his students develop new methods for the construction of novel heterocyclic molecules using chemistry known as oxidative dearomatizing spiro-cyclization. In this research, the dearomatization process is linked with a second chemical transformation leading to tandem reaction processes. Such sequential transformations permit the experimentalist to achieve a rapid increase in molecular complexity in one synthetic operation. Such tactics provide advantages in terms of synthetic efficiency and reduction in the cost of resources. Specifically, this work examines the oxidative cyclization of guanidines, thioureas, and ureas both in terms of the reaction scope but also to provide a detailed mechanistic understanding of the process. Two natural products have been identified to test the limits of the proposed chemistry by taking advantage of the efficiency gains. Both targets are secondary metabolites isolated from marine invertebrates which have yet to succumb to total synthesis efforts and may serve as lead compounds in medicinal chemistry investigations. The tandem reactions being investigated in the course of this work provide rapid access to the core structural features of these molecules. Broader impacts of this work include the recruitment and training of the next generation of scientists, including members of groups that are under-represented in the chemical sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学系的化学合成计划正在支持德克萨斯大学阿灵顿分校的卡尔·洛夫教授的研究，与本科生和研究生一起开发构建复杂有机结构的新方法，例如那些可能用于化学生物学或药物化学研究的方法。在目前的研究中，正在发明新的方法和策略，以允许通过串联反应组装复杂的分子框架，以提高合成效率。 串联反应涉及两个或多个化学反应的顺序，使得第一个反应建立第二个反应，以此类推。这种策略有可能通过减少过程中所需的合成步骤的数量来提高效率，从而减少有机溶剂的使用和所需的纯化步骤的数量。 计划概述了应用新的方法来合成两种天然产品最初从海洋无脊椎动物分离。 这些天然产物由于其不寻常的双环结构而受到关注。这些具有挑战性的目标结构既激发了方法学的灵感，又被认为具有化学生物学研究的潜力。 特别是，有一个项目是专门为高中生的参与而设计的。 在后一种情况下，学生有机会做有机合成的研究，否则将无法提供给他们。Lovely教授和他的学生开发新的方法，用于使用化学称为氧化脱芳构化螺环化的新杂环分子的建设。 在这项研究中，脱芳构化过程与导致串联反应过程的第二化学转化相关联。 这种连续的转变允许实验者在一次合成操作中实现分子复杂性的快速增加。这种策略在综合效率和资源成本降低方面提供了优势。 具体而言，这项工作研究的氧化环化胍，硫脲和脲的反应范围，但也提供了一个详细的机械理解的过程。 已经确定了两种天然产物，以利用效率增益来测试所提出的化学品的限制。 这两个目标是从海洋无脊椎动物中分离的次级代谢产物，尚未屈服于全合成的努力，并可能作为药物化学研究的先导化合物。 在这项工作的过程中正在研究的串联反应提供了快速访问这些分子的核心结构特征。 这项工作的更广泛的影响包括招募和培训下一代科学家，包括在化学科学中代表性不足的团体的成员。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Dearomatizing spirocyclization of thioureas, ureas and guanidines

• DOI: 10.1016/j.tetlet.2021.153054
• 发表时间: 2021-04
• 期刊: Tetrahedron Letters
• 影响因子: 1.8
• 作者: Marian N. Aziz;Ravi P. Singh;D. Gout;C. J. Lovely

Ene reactions of pre-aromatic heterocycles – Oxazoles

前芳香杂环的烯反应 - 恶唑

• DOI: 10.1016/j.tetlet.2021.153134
• 发表时间: 2021
• 期刊: Tetrahedron Letters
• 影响因子: 1.8
• 作者: Singh, Ravi P.;Fulton, Brandon B.;Phan, Huy T.;Gout, Delphine;Lovely, Carl J.
• 通讯作者: Lovely, Carl J.

Liquid chromatography enantiomeric separation of chiral ethanolamine substituted compounds

手性乙醇胺取代化合物的液相色谱对映体分离

• DOI: 10.1002/chir.23419
• 发表时间: 2022
• 期刊: Chirality
• 影响因子: 2
• 作者: Firooz, Sepideh Khaki;Putman, Joshua;Fulton, Brandon;Lovely, Carl J.;Berthod, Alain;Armstrong, Daniel W.
• 通讯作者: Armstrong, Daniel W.

Novel thiazolidines of potential anti-proliferation properties against esophageal squamous cell carcinoma via ERK pathway

• DOI: 10.1016/j.ejmech.2022.114909
• 发表时间: 2022-12-09
• 期刊: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 6.7
• 作者: Aziz，Marian N.;Nguyen，Linh;Lovely，Carl J.
• 通讯作者: Lovely，Carl J.