Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are required to improve its antifungal activity. Our work in this paper focused on the replacement of oxazole ring in streptochlorin with the imidazole ring, to discover novel analogues. Based on this design strategy, three series of streptochlorin analogues were efficiently synthesized through sequential Vilsmeier-Haack reaction, Van Leusen imidazole synthesis and halogenation reaction. Some of the analogues displayed excellent activity in the primary assays, and this is highlighted by compounds 4g and 4i, the growth inhibition against Alternaria Leaf Spot and Rhizoctorzia solani under 50 μg/mL are 97.5% and 90.3%, respectively, even more active than those of streptochlorin, pimprinine and Osthole. Molecular docking models indicated that streptochlorin binds with Thermus thermophiles Leucyl-tRNA Synthetase in a similar mode to AN2690, offering a perspective on the mode of action study for antifungal activities of streptochlorin derivatives. Further study is still ongoing with the aim of discovering synthetic analogues, with improved antifungal activity and clear mode of action.

链绿素是一种从海洋链霉菌属中分离的吲哚生物碱小分子，在我们之前的研究中，由于其在预防许多植物病原体方面具有强大的生物活性，因此它是一种很有前途的先导化合物，但需要进一步的结构修饰以提高其抗真菌活性。我们在本文中的工作重点是用咪唑环取代链绿素中的恶唑环，以发现新的类似物。基于此设计策略，通过连续的 Vilsmeier-Haack 反应、Van Leusen 咪唑合成和卤化反应，高效合成了三个系列的链绿素类似物。一些类似物在初步分析中显示出优异的活性，化合物4g和4i突出显示了这一点, 50 μg/mL 下对链格孢属叶斑病和立枯病菌的生长抑制率分别为 97.5% 和 90.3%，甚至比链绿素、pimprinine 和 Osthole 更有效。分子对接模型表明，链绿素与嗜热菌Leucyl-tRNA 合成酶的结合方式与AN2690 相似，为链绿素衍生物抗真菌活性的作用模式研究提供了一个视角。进一步的研究仍在进行中，目的是发现合成类似物，具有更好的抗真菌活性和明确的作用模式。