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

职业：通过分子内 C-H 插入合成桥联多环天然产物

• 批准号: 1352439
• 负责人: Jeremy May
• 金额: $ 60万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352439&HistoricalAwards=false
• 关键词: CAREER; Synthesis; Bridged; Polycyclic; Natural

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.

通过这一奖项，在化学系化学合成计划的支持下，休斯顿大学的Jeremy A.May教授正在开发一种通用的方法，用于各种具有生物活性的桥联多环天然产物的化学合成。虽然这种结构在过去需要不同的战略方法，但级联反应序列的使用有效地为各种此类分子提供了对分子键的控制。高活性的卡宾中间体、共价连接的碳-碳三键和二聚体催化剂允许在一次反应中合成多个化学键，包括高度应变的环结构。由于反应序列通过C-H键插入形成其最终的化学键，因此不需要事先对插入位置的底物进行修饰，这大大提高了效率，最大限度地提高了灵活性，并最大限度地减少了浪费。反应活性的控制因素正在研究中，新的转化催化剂正在设计中。通过这种合成技术产生的结构基序在大量自然产生的微量生物活性化合物中找到。由于这些天然产物表现出抗疟疾、抗癌、抗菌和其他有用的性质，合成策略正被应用于这些目标，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改，从而可以识别生物活性的关键分子元素。因此，这一努力对疾病机制、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整合了多个层次的教育，参与的研究生、本科生和初中生学习生物化学、有机化学、药物化学、催化和科学分析的原理。