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

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 H-1 NMR,C-13 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 50 mu g/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 9.77 mu g/mL, respectively. The EC50 of compound 3c - 08 against Colletotrichum camalliae Massee and Pestalotiopsis theae (Sawada) Steyaer were 9.17 and 8.83 mu g/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 preliminary results of insecticidal activity showed that the insecticidal activity of these compounds against Myzus persicae was normal at a concentration of 400 mu g/mL. In conclusion, these results laid a foundation for further development and utilization of sanguinarine derivatives.