Qi Xubing, Jaiswal Yogini, Xie Xinrong, Fan Yu, Wu Rongping, Su Shaoyang, Guan Yifu, Williams Leonard, Song Xun
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China.
Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, The North Carolina Research Campus, Kannapolis, NC 28081, USA.
Molecules. 2025 Mar 31;30(7):1546. doi: 10.3390/molecules30071546.
Canthin-6-one alkaloids have consistently attracted the interest of medicinal chemists due to their wide range of promising bioactivities, including antitumor, antifungal, antibacterial, and antiviral properties. However, their low natural abundance in plants has constrained the further exploration of their potential bioactivities. This study reports a comprehensive synthesis of canthin-6-one alkaloids, utilizing key Suzuki coupling and Cu-catalyzed amidation reactions to construct their core scaffold. Derivatives were synthesized with Koenig-Knorr glycosylation for the further modification of synthetic canthin-6-ones. The antimicrobial activities of the synthesized compounds were evaluated against , , and using the micro-dilution method. In total, 17 compounds were synthesized, including nine canthin-6-ones. Notably, alkaloids , , and - were prepared for the first time, along with 8 new derivatives. Their structures were confirmed by NMR and MS analyses. At 50 µg/mL, the alkaloids - and exhibited antimicrobial properties against , and . The antimicrobial activity of alkaloids , - and - against these four microbial human pathogens is reported here for the first time. Overall, this research not only advances our understanding of canthin-6-one alkaloid synthesis, but also provides a foundation for developing novel compounds with pharmaceutical properties.
由于具有广泛的潜在生物活性，包括抗肿瘤、抗真菌、抗菌和抗病毒特性，铁屎米 - 6 - 酮生物碱一直吸引着药物化学家的关注。然而，它们在植物中的天然丰度较低，限制了对其潜在生物活性的进一步探索。本研究报道了铁屎米 - 6 - 酮生物碱的全合成，利用关键的铃木偶联反应和铜催化的酰胺化反应构建其核心骨架。通过柯尼希 - 克诺尔糖基化反应合成衍生物，用于对合成的铁屎米 - 6 - 酮进行进一步修饰。采用微量稀释法评估合成化合物对金黄色葡萄球菌、大肠杆菌、白色念珠菌和黑曲霉的抗菌活性。总共合成了17种化合物，包括9种铁屎米 - 6 - 酮。值得注意的是，生物碱A、B、C和D首次制备，还有8种新衍生物。通过核磁共振和质谱分析确认了它们的结构。在50μg/mL时，生物碱E和F对金黄色葡萄球菌、大肠杆菌和白色念珠菌表现出抗菌性能。本文首次报道了生物碱G、H和I对这四种人类致病微生物的抗菌活性。总体而言，这项研究不仅推进了我们对铁屎米 - 6 - 酮生物碱合成的理解，也为开发具有药物特性的新型化合物奠定了基础。
