Synthesis And Fungicidal Evaluation Of 1,3,9-Multiple Substituted-Carboline Derivatives

?-carboline alkaloids are a kind of important natural products with a wide range of biological activities,and it has been a focus due to their high efficiency in antibacterial,anti-tumor,anti-virus,anti-malaria and other activities.Quantities of research have shown that?-carboline alkaloids have outstanding antitumor activity,but because of their own toxicity,they have not been applied in clinical until now.Therefore,we have developed a new way to study the antibacterial ability of this kind of alkaloids and developed a series of novel fungicides with independent intellectual property rights,low toxic and side effects.This study based on our previous work as well as a large of literature reviews and designed the compounds according to the combination principles,aimed to synthesize and modify the framework of?-carbazoline and evaluate the antibacterial activity of the target compounds in vitro.It is expected to provide canditate compounds for new fungicides with high antibacterial activity,screened out from the series of?-carbazoline derivatives we designed.In the second chapter,two series of 1,2,3-triazole-?-carboline derivatives were synthesized from L-tryptophan and Harmine via multi-step reaction.In chapter three,two series of benzimidazole-?-carbazoline derivatives were synthesized by Pictet-Spengler reaction,aromatization,alkylation and oxidation from L-tryptophan.In the fourth chapter,the key intermediate,from the above chapter,are raw materials,and reacted with o-aminothiophenal to obtain two series of benzothiazole-?-carbazoline.The target products synthesized in the above three chapters are all new compounds,which was identified by ¹H NMR,¹³C NMR,HRMS and melting piont,respectively.Using mycelium growth rate method,all the compounds were tested on the antibacterial activities in vitro against the five fungus:Fusarium oxysporum,Rhizoctorzia Solani,Botrytis cinereal Pers,Sunflower sclerotinia rot,Rape sclerotinia rot.A total of 60 compounds were synthesized in this study and the preliminary results showed that most compounds exhibit high inhibiting effect against Sunflower sclerotinia rot,especially X7r,better than that of the control drugs carbendazim and azoxystrobin.1-substituted-?-carboline derivatives are benefical for inhibition of Rhizoctorzia Solani and Rape sclerotinia rot,while 3-substituted-?-carboline derivatives are more suitable for Fusarium oxysporum and Botrytis cinereal Pers.It's worth mentioning that compound Y2g has shown outstanding antibacterial activity,the inhibition rate is 100%at 50?g/mL,against Botrytis cinereal Pers.Specifically,compound H9b and Y2c exhibited broad-spectrum fungicidal activity against most of the tested fungi.In conclusion,a number of novel compounds with excellent antibacterial activity were obtained by introducing 1,2,3-triazole,benzimidazole and benzothiazole groups into the skeleton of?-carboline,which enriched the database of antimicrobial drugs and laid a foundation for the development of new fungicides.