Synthesis And Antifungal Activities Of 2-Aryl-3,4-Dihydro-γ-Carbolines-2-Iums

Alkaloids are a class of secondary metabolism composition with wide range of species, complex structures and multiple significant pharmacological activities. Carbolines are an important subclass of alkaloid. Carbolines are pyridoindoles and form a very heterogeneous group of substances that can be divided into α-, β-, γ- and δ-carbolines, depending on the position of the nitrogen in the pyridine ring. β-carbolines occur as a major source of carbolines which was proven having remakable anticancer, antimicrobial, parasiticidally, antifungal, antioxidant activity and so on. Since α-, γ- and δ-carbolines are rarely present in the environment, little is known about their functions.The study on which the structure-activity relationship of iminium bond-contained isoquinolines(IBCIQs) showed that C=N+ is the active site of biological activity such as anticancer, antibacterial, acaricidal and other pharmacological activity. A series of 2-aryl-3,4-dihydro-γ-carbolines with the same active site C=N+ as IBCIQs were designed and synthesized. Then the in vitro bioactivities and structure-activity relationship(SAR) were systematically evaluated to plant pathogenic fungi. The objective of this research was to search and find carbolines medicine with higher activities, and build theoretical foundation to subsequent structural optimation and medicinal development.The most important result of this research is listed below:1. A new route was established which was used to synthesize 2-aryl-3,4-dihydro-γ-carboline-2-iums with Indole-2-carboxylic acid as the starting material.2. Ten compounds of 2-aryl-3,4-dihydro-γ-carboline-2-iums were designed with the strategy of bionics and synthesized. The compounds were structurally characterized on the base of analysis of 1H NMR and 13 C NMR.3. In this study, ten title compounds with various substituents on the 2-phenyl ring were evaluated for bioactivity against twelve phytopathogenic fungi using the mycelial growth rate method and their SAR discussed.The results showed that almost all the compounds showed definite activities in vitro against each of the test fungi at 150 μmol/mL. All the compounds were found to be more active than thiabendazole(TBZ) on Alternaria solani and Pyricularia grisea. For Alternaria alternate, all the compounds except RK-1(R = H) and RK-10(R = p-OMe) were more active than the TBZ; For Curvularia lunata, all the compounds except RK-1(R = H), RK-4(p-F) and RK-10(p-OMe) were more active than the TBZ.The SAR is as follows: the 2-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electrondonating substituents cause a decrease of the activity. In most cases, oara-halogenated isomers were more active than the corresponding meta- and para-halogenated isomers.Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals.