New Methods for Heterocycle Synthesis

通过该奖项，化学系化学合成项目支持德克萨斯大学阿灵顿分校Carl Lovely教授与本科生和研究生合作开发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，人们正在发明新的方法和策略，通过串联反应来组装复杂的分子框架，以提高合成效率。串联反应包括两个或两个以上化学反应的顺序，例如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工艺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。计划将新方法应用于两种天然产品的合成，这些天然产品最初是从海洋无脊椎动物中分离出来的。这些天然产物由于其不寻常的双环结构而引起人们的兴趣。这些具有挑战性的目标结构既启发了方法，也被认为具有化学生物学研究的潜力。从这个项目中获得的额外好处包括招募和参与代表性不足的高中、本科生和研究生。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，学生有机会进行有机合成方面的研究，否则他们将无法获得这些研究。洛夫里教授和他的学生开发了新的方法来构建新的杂环分子使用化学称为氧化去芳化螺环化。在本研究中，脱芳过程与导致串联反应过程的第二次化学转化相关联。这种顺序变换使实验人员能够在一次合成操作中迅速增加分子的复杂性。这种策略在综合效率和降低资源成本方面具有优势。具体地说，这项工作考察了胍、硫脲和脲的氧化环化反应范围，同时也提供了对该过程的详细机制理解。已经确定了两种天然产物，通过利用效率增益来测试所提议的化学的极限。这两种靶点都是从海洋无脊椎动物中分离出来的次生代谢物，尚未完全合成，可作为药物化学研究中的先导化合物。在这项工作中所研究的串联反应提供了对这些分子的核心结构特征的快速访问。这项工作的更广泛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群体的成员。该奖项反映了美国国家科学基金会的法定使命，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。

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.