Design And Synthesis Of α-dicarbonyl Derivatives And Its Antibacterial Activity Against Anthracnose Of Cunninghamia Lanceolata

Cunninghamia lanceolata,the native tree species in China,has important application values and medicinal values.Anthracnose is one of common and most serious disease on Cunninghamia lanceolata.At present,there are two main control measures of Cunninghamia lanceolata anthracnose,namely chemical and silvicultural control.Some broad-spectrum fungicides are usually used in the chemical control of Cunninghamia lanceolata anthracnose.In recent years,organic small molecule fungicides are developing rapidly.Scientists have synthesized and studied various types of compounds through different methods aimming to quickly find high-efficiency,low toxicity and environment-friendly candidate compounds for medical or agricultural use.Nevertheless,there are only few small molecular compounds have been developed about Cunninghamia lanceolata anthracnose.α-Dicarbonyl compounds are the core skeleton of many natural products and drugs,which have been extensively applied in the fields of pesticides and medicine,such as antibacterial,antiviral,insecticidal,weeding,anti-inflammatory,anti-cancer and anti HIV.This paper mainly focuses on synthesis and derivatization ofα-Dicarbonyl compounds,and their structures were identified and characterized by NMR,single crystal or mass spectrometry.The anti-anthracnose activities of synthetic compounds were also studied through primary and secondary screening for a total of 53 effective compounds of three types,including 6 compounds of MCP derivatives,21 compounds of alkynyl sulfones derivatives,and 21 compounds ofα,α-dihaloketones derivatives.Among them,the antibacterial rates of 29compounds with good activity were calculated and studied,and the antibacterial rate of 6compounds can reach 100%with concentration of 50μg/m L.In this thesis,MCPα-dicarbonyl containing sulfur ether or sulfoxide,α-ketoamides,and benzyl cyano phthalates synthesized from ninhydrin and alcohol were designed and synthesized and their anti-anthracnose activity of Cunninghamia lanceolata was studied,respectively.The thesis can be divided into the following parts:（1）A novel and efficient synthetic method for preparing disubstitutedα-dicarbonyl from the reaction of renewable plant extract 3-methyl cyclopenten-1,2-dione（MCP）and sulfoxide in the presence of trifluoroacetic anhydride and dichloroethane was developed.This method not only provides a new stratgy compared to the existing methods,but also features high yield and wide applicability of substrates.Further,it has more advantages over the tranditional method with using expensive transition metal catalyst,high reaction temperature as well as complicated procedures.（2）A series of polysubstitutedα-dicarbonyl were produced by sequential reaction of renewable plant extract 3-methyl cyclopenten-1,2-dione（MCP）with sulfoxide in the presence of trifluoroacetic anhydride and dichloroethane.The method provides strong support for the development and preparation of natural products with mild conditions,no metal catalysis,simple operation and wide range of substrates.（3）A green,simple and efficient synthetic method of alkynyl sulfones under electrochemical conditions was developed.A series of alkynyl sulfones were prepared from renewable plant extract 3-methyl cyclopenten-1,2-dione（MCP）and simple alkynes under electrochemical conditions.Under the optimized conditions,the electrolyte is potassium iodide（1.0 equivalent）in acetonitrile/water（10 m L/0.1 m L）at room temperature,platinum electrodes as the cathode and anode,and the constant current electrolysis current is 10 m A for 7 hours,the desired product alkynyl sulfone 3.3aa is obtained in 93%yield.This method realizes the reaction at room temperature without metal catalysis and post-treatment,achieving good applicability and wide range of substrate.In addition,the reaction mechanism was also studied in detail.（4）A new method for the efficient synthesis of 2-（cyanomethyl）benzoate esters from alcohols and indandione compound was studied.The optimized reaction conditions are indandione compound reacted with ethanol（0.1 M）for 24 hours with diethylamine as base.The separation yield of the expected product 4.3aa was 90%.It is found that various natural alcohols such as cinnamyl alcohol,pepper alcohol,furfuryl alcohol,as well as plant essential oil alcohols including citronellol,tetrahydro geraniol,geraniol,perilla alcohol and neroli alcohol,other abietic alcohol from natural rosin and modified cholestanol,were successfully transformed into the expected products.This method is simple and efficient and the conversion of various substrates with high yield could be obtained by adding equivalent alkali.Meanwhile,it is suitable for gram-scale reaction.Later research found that the use of alkali can be avoided under electrochemical conditions,and the reaction can be carried out smoothly by adding electrolyte.（5）An electrochemical oxidation dihalogenation reaction using CHCl₃,CH₂Cl₂,Cl CH₂CH₂Cl and CH₂Br₂ as halogen sources at room temperature for the synthesis ofα,α-dihaloketones was studied.The method has the advantages of simple operation,easy amplification,mild reaction condition,avoiding the use of conventional toxic halogenation reagents,etc.Various valuableα,α-dihaloketones owning great industrial application value can be synthesized from readily available alkynes by using this environmentally friendly method that provides a simple solution for late-stage functionalization.（6）A new electrochemical method for the synthesis of 2,3-diaminoindoles was developed.Indoles are a very important class of compounds and their synthesis has always been a hot and difficult issue.This method provides a new electrochemical strategy for the triamination of alkynes to controllably access various 2,3-diaminoindoles under mild conditions.TEMPO was used as the redox catalyst for the reaction at room temperature,avoiding terminal oxidant,transition metal and misuse of explosive reagent.Another synthetic method was established for the synthesis ofα-ketoamides with indole compounds as raw materials.Given the simple,metal-free,room-temperature reaction conditions,it expands the synthesis path of ketoamides and their late-stage functionalization.（7）We mainly studied the bioactivity of the synthesized compounds against anthracnose of Cunninghamia lanceolata and found that 51 effective compounds of three types have bioactivity.The antibacterial rate of 29 compounds with good activity were calculated subsequently.Among them,α,α-dihaloketones have the best antibacterial activity under the concentration of the compound was 50μg/m L,the antibacterial rate of 5.3c,5.3f,5.3g,5.3h,5.3i,5.2i compounds can reach 100%,which was significantly better than the control technical drugs Thiram（51.5%）and chlorothalonil（39.5%）at the same concentration.The second is alkynyl sulfones that the antibacterial rate of 3.3ae compound can reach 71%with a compound concentration of 80μg/m L,which was significantly better than the control technical drugs Thiram（56.8%）at the same concentration.The highest antibacterial rate of o-diketones is 66%when the concentration of2.24 compound was 250μg/m L.To improve the antibacterial rate,different active groups is suggeseted to be introduced base on the above results,which could provide important theoretical support for the creation of new drugs in the future.