CAREER: Synthesis of Bridged Polycyclic Natural Products via Intramolecular C-H Insertion

通过这个奖项，由化学系的化学合成计划，教授杰里米A。休斯顿大学的May正在开发一种化学合成多种具有生物活性的桥连多环天然产物的通用方法。虽然过去这样的结构需要不同的策略方法，但级联反应顺序的使用有效地为各种这些分子提供了对分子键合的控制。高反应性卡宾中间体、共价连接的碳-碳三键和二聚铑催化剂允许在一个反应中合成多个化学键，包括高度应变的环状结构。由于反应序列通过C-H键插入形成其最终化学键，因此不需要在该插入位点处对基底进行预先修饰，这大大提高了效率，使灵活性最大化，并使浪费最小化。控制反应性的元素正在研究中，用于转化的新催化剂正在设计中。通过这种合成技术产生的结构基序存在于大量自然产生的微量生物活性化合物中。由于这些天然产物显示出抗疟疾、抗癌、抗菌和其他有用的特性，因此合成策略正被应用于这些靶点，以获得足够的材料用于进一步研究。此外，化学合成的快速性质允许对母体结构进行修饰，以便可以鉴定生物活性的关键分子元件。因此，这项工作对疾病机制，天然产物生物学和化学的几个领域产生了更广泛的影响。该奖项下的研究工作是在多个层次的教育集成，作为研究生，本科生和初中学生谁参与学习生物化学，有机化学，药物化学，催化和科学分析的原则。

Through this award, supported by the Chemical Synthesis Program of the Division of Chemistry, Prof. Jeremy A. May of the University of Houston is developing a general method for the chemical synthesis of a variety of biologically active bridged polycyclic natural products. While such structures in the past have required disparate strategic approaches, the use of a cascade reaction sequence efficiently provides a variety of these molecules with control over the molecular bonding. Highly reactive carbene intermediates, carbon-carbon triple bonds that are covalently linked, and dimeric rhodium catalysts allow multiple chemical bonds, including highly strained cyclic structures, to be synthesized in one reaction. As the reaction sequence forms its final chemical bond through a C-H bond insertion, no prior modification of the substrate at the site of this insertion is required, which greatly increases efficiency, maximizes flexibility, and minimizes waste. The controlling elements for the reactivity are under study, and new catalysts for the transformation are being designed.The structural motifs produced by this synthesis technology are found in numerous biologically active compounds produced naturally in minute quantities. Since these natural products display antimalarial, anticancer, antimicrobial, and other useful properties, the synthetic strategy is being applied to these targets to obtain sufficient material for further study. Moreover, the rapid nature of the chemical synthesis allows modifications to the parent structure to be made so that the key molecular elements for biological activity may be identified. Thus, this effort has a broader impact on disease mechanisms, natural product biology, and several fields of chemistry. The research effort under this award is integrated in multiple levels of education, as the graduate, undergraduate, and junior high students who participate learn principles of biochemistry, organic chemistry, medicinal chemistry, catalysis, and scientific analysis.