中文摘要：

目的 通过简单快速的有机催化,在温和反应条件下,合成一系列新型的广藿香酮衍生物3a-3m,并考察其体外抗菌活性。方法 基于具有抗菌活性的广藿香酮,在课题组前期对其作用机制的研究基础上,利用绿色高效的有机催化策略,设计并合成一系列具有共轭结构侧链的广藿香酮衍生物。经过条件筛选,确定了最佳反应条件,通过柱层析能够快速分离得到目标产物,并通过核磁共振、高分辨质谱和单晶衍射等分析方法确定化合物结构。结果 在筛选的最优条件下,在广藿香酮侧链进行了一系列具有不同电子效应和位阻效应的结构修饰,目标产物分离收率最高可达91%。最后,考察了该系列衍生的抗菌活性,得到一个有应用前景的先导化合物。结论 广藿香酮是具有多种生理活性的中药药效物质,其在医药领域有着极其重要的学术价值,该化合物的构效关系和结构修饰研究是中药化学的热点方向之一。通过本研究,可以高效地制备一系列广藿香酮衍生物,对开发新的抗菌药物具有启示作用和参考价值。

英文摘要：

Objective To develop a facile synthetic method that enables the efficient synthesis of pogostone derivatives via organocatalysis under mild reaction conditions and to screen the antibacterial activities in vitro. Methods Based on the antibacterial activity of pogostone and the mechanism study in our lab, a series of new pogostone derivatives bearing conjugated functional groups were designed and smoothly synthesized via an organocatalytic strategy. After the screening studies, the optimal reaction condition was determined and the desired products were obtained by flash column chromatography. The structures of all compounds were further confirmed by the NMR analysis, the HRMS analysis and the single crystal diffraction. Results Under optimal reaction conditions, this study synthesized a variety of derivatives with diverse electronic and steric modifications on the side chain of the pogostone core, and the isolated yield was up to 91%. This study also screened the antibacterial activities of these derivatives in vitro, and a promising lead compound was obtained. Conclusion Pogostone is a small organic molecule with diverse potential bioactivities, and this compound and related derivatives strongly attract the academic society of pharmaceutical science. As a result, the research on the structure-activity relationship of pogostone and the development of new synthetic methods to manufacture the pogostone derivatives have also been interesting topics in both medicinal and organic chemistry. Herein, we report a mild and practical method to address this issue. This methodology could enable us to provide a wide range of new pogostone derivatives, and the results played a positive role and had reference values for the future research, especially in the development of new antibacterial agents.