Synthesis And Acaricidal Activity Evaluation Of Curcumin Derivatives

Curcumin is the main active ingredient of turmeric,which has been widely used to treat diabetes liver disease,rheumatoid,arthritis,atherosclerosis,infectious diseases and cancer because of its pharmacological activities,such as antibacterial,anti-oxidation,anti-inflammatory,anti-tumour, anti-HIV virus.Therefore,the relevant research using curcumin as a leading template for structural transformation,modification and designing new analogues has widely drawn chemists' and pharmacologists' attention.The research using crucumin as a leading compound to design and synthesize has shown that most of the derivatives have good biological activities,and even better than curcumin.But it is usually the report of medicinal research,which can be hardly applied to the research and exploration of agricultural activity.The preliminary laboratory studies have shown that curcumin and its similar compounds have the good acaridal activity,which has potential application value to control the agricultural mites.Thus,this study selects curcumin as a template compound and modifies its structure,and tries to discover the substance possessing high acaridal activity in the novel derivatives,which can lay a theoretical foundation for the creation of new acaricides,and also has important practical significance.1.Synthesis of curcumin- derivativesThe curcumin molecule includes the special structure which has not only the aromatic ring but also the,1,6 - heptadiene -3,5 - dione,the latter one may be regarded as the B area that contains the olefinic bond,double black ewe base and active methylene.Base on the character of functional group,the derivatives are designed and synthesized in order to research the structure active relationship further.Natrual active curcumin contains the two-a,β-unsaturated carbonyl(-C=C-C=O).It can be oxided with t-BOOH to form epoxy derivatives;the carbonyl structure can be reduced to produce the diol derivatives,and then added into the thionyl chloride,occurred chlorophthalic derivatives; Methylene on lively,reaction with 1,2-dibromoethane to produce the alkylation derivatives There are 7 derivatives have been synthesized in the B district,the structure is confirmed through infrared spectroscopy(IR),nuclear magnetic resonance(NMR),elemental analysis(EA). The result shows that five new compounds(4-(3,5-dichloro-7-(4-bydroxy-3-methoxyphenyl) hepta-1,6-dienyl)-2-methoxyphenol,1,3-bis(3-(4-hydroxy-3-methoxyphenyl)oxiran-2-yl)propane-1,3 -dione,4-(2-bromoethyl)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione,4,4-bis(2-br omoethyl)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione,1,7-bis-(3- methoxy -4-hydroxyphenyl) -4,4-(Central ethyl)-1,6 - heptadiene -3,5 - dione) are reported at the first time.Apart from lower activity of epoxy derivative,all of other compounds have good acaricidal bioactivity.2.Isolation and purification of curcumin-diphenylhydrazoneThe column chromatography on silica gel is used to isolate and purify the target compound.The effect of different product model of silica gel,flow rate and eluting agent on the isolation and purification of curcumin- derivatives are investigated.Silica gel 100-200 mesh is chosen to separate the derivatives of curcumin;the optimal flow rate is 1mL/2min;and eluting agent is ethyl acetate/petroleum ether mixture.The washing out process is repeated two or three drops and the compound are recrystallized from ethyl acetate with little ether to give a red needle crystal.3.Evaluation of the bioactivity of the Curcumin derivatives against Tetranychus cinnabarinusContrasting the curcumin and the 95%Pyridaben,this research evaluates the acaricidal bioactivity of curcumin derivatives against Tetranychus cinnabarinus.It shows the relationship among the activities as follow:Double chlorided derivatives＞alkylated derivatives(A＞B＞C)＞Two-carbonyl reducted derivatives＞the double bond reducted derivatives＞ epoxidation curcumin derivatives;in which chloro-2-derivative shows good Binapacryl activity,treatment after 24h and 48h,the LC₅₀ are 0.2668mg/mLand 0.1550mg/mL respectively..In the alkylated derivatives CM01 has the best activity,treatment after 24h and 48h,the LC₅₀ are 0.0605mg/mL and 0.0191mg/mL respectively.However,the LC₅₀ of the Pyridaben against the Tetranychus cinnabarinus are 0.0605mg/mL in 24h and 0.0191 mg/mL in 48h.the activity differences is about five times;At the same time,the results also Show that,with the exception of Central oxide,the activities of other curcumin derivatives in all periods are higher than those of curcumin,which indicates the synthetic derivative of curcumin has researching significance.However,the contact activity of Tetranychus cinnabarinus of the seven derivatives is lower than that of Pyridaben.As for the change of the new structure about curcumin molecule and its derivatives blinding to the target,there is no conclusion and it needs further study.