6-N杂环取代血根碱衍生物的合成、结构表征、生物活性与构效关系  

Synthesis,Characterization,Biological Activity and Structure-activity Relationship of 6-N-heterocyclic Substituted Sanguinarine Derivatives

作　　者：贾长青 马瑞 钱玺丞 覃兆海[2] 许厚强[3] JIA Changqing;MA Rui;QIAN Xicheng;QIN Zhaohai;XU Houqiang(National Engineering Research Center,Tongren Polytechnic College,Tongren 554300,China;College of Science,China Agricultural University,Beijing 100193,China;Postdoctoral Research Mobile Station in Biology,Guizhou University,Guiyang 550000,China)

机构地区：[1]铜仁职业技术学院,国家工程研究中心,铜仁554300 [2]中国农业大学理学院,北京100193 [3]贵州大学生物学博士后科研流动站,贵阳550000

出　　处：《高等学校化学学报》2023年第11期55-65,共11页Chemical Journal of Chinese Universities

基　　金：贵州省科技计划项目(批准号:黔科合基础[2018]1422);贵州省高校创新团队(批准号:黔教技[2023]097)资助。

摘　　要：以血根碱为先导,通过活性基团拼接方法,设计合成了一类结构新颖的6-N杂环取代血根碱衍生物.目标化合物的结构均通过核磁共振波谱(NMR)、红外光谱(IR)和高分辨质谱(HRMS)确证.采用生长速率法测定了目标化合物的体外抑菌活性,并对其构效关系进行了分析.初步抑菌活性测试结果表明,目标化合物3a-06,3a-07, 3b-01, 3c-07和3c-08对10种供试病原菌表现出相对广谱的抑菌活性,在50μg/mL浓度下,对多数供试病原菌抑制率在72%以上.精密毒力测定结果显示,部分目标化合物表现出优良的抑菌活性.化合物3b-01对茶叶炭疽病菌和棉花立枯病菌的半最大效应浓度(EC_(50)值)分别为8.52和9.77μg/mL;化合物3c-08对茶叶炭疽病菌和茶叶轮斑病菌的EC_(50)值分别为9.17和8.83μg/mL,具有在茶叶病害防治方面应用的潜力.与先导化合物血根碱盐酸盐相比,多数目标化合物表现出较优的抑菌活性.杀虫活性初步测定结果表明,在400μg/mL浓度下该类化合物对桃蚜的杀虫活性一般.本文为血根碱衍生物的进一步开发利用提供了一定依据.A novel series of 6-N-heterocycle substituted sanguinarine derivatives was designed and synthesized by active group splicing with sanguinarine as lead.The structures of title compounds were confirmed by 1H NMR,13C NMR,IR and HRMS.By using the mycelium growth rate method,title compounds were evaluated for antifungal activities in vitro and structure-activity relationships(SAR)were investigated.The preliminary antifungal activity test results indicate that compounds 3a-06,3a-07,3b-01,3c-07 and 3c-08 exhibited a relatively broad spectrum of fungicidal activity against ten tested pathogens at a concentration of 50μg/mL,the inhibition rate against most of the tested pathogens is above 72%.In further precision virulence assay,some title compounds showed good antifungal activity.The median effective concentrations(EC50)of compound 3b-01 against Colletotrichum camalliae Massee and Thanatepephorus cucumeris were 8.52 and 9.77μg/mL,respectively.The EC50 of compound 3c-08 against Colletotrichum camalliae Massee and Pestalotiopsis theae(Sawada)Steyaer were 9.17 and 8.83μg/mL,respectively.Compound 3c-08 has the potential for application in the prevention and control of tea diseases.Compared with the lead compound sanguinarine hydrochloride,most of the title compounds showed better antifungal activity.The prelim-inary results of insecticidal activity showed that the insecticidal activity of these compounds against Myzus persicae was normal at a concentration of 400μg/mL.In conclusion,these results laid a foundation for further development and utilization of sanguinarine derivatives.

关 键 词：博落回 血根碱衍生物 N杂环 生物活性 构效关系 

分 类 号：O626[理学—有机化学]