Synthesis And Biological Activity Of Carbolines And Thiazole-containing Phenoxyacetic Acid

Herbicide,an important type of pesticides,palys an important role in weeds controlling and safe food production.After more than 100 years of development,great progress has been made in chemical herbicide,and weeds have been controlled effectively.However,due to the limited number of herbicides and the limited modes of action,increasing risistance has emerged while long-term use of herbicides that are of single mode of action.Along with people’s growing awareness of environmental protection,it is urgent to develop highly efficient,low-toxic,highly selective,and environmentally friendly herbicides.In this paper,.tetrahydro-β-carbolines and thiazole-containing phenoxyacetic acid are designed and synthesed.All target compounds were characterized by 1H NMR,13C NMR,HRMS,etc.Besides,their bioactivities was tested.The details of this thesis are as follows:1.First,the general strategies for the study of lead compounds were outlined.Then the research progress of the MEP pathway and its key enzyme IspD was summarized.Then synthetic methods of the tetrahydro-β-carbolines and inhibitors of the IspD enzyme,and the research progress in anti-plasma parasites were summarized.Besides,synthetic methods their herbicidal activities of benzothiazoles,amides,phenoxyacetic acids were summarized.2.Synthesis of tetrahydro-β-carbolines.The synthetic method is as follows:methyl 1-(substituted-phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylates are synthesized by Pictet-Spengler reaction from L-tryptophan methyl ester and a series of substituted benzaldehydes,the relative configuration of each compound was determined by 13C NMR spectroscopy,using the empirical rule of Cook.The target compounds tetrahydro-β-carbolines were abtained by hydrolyzing the ester groups and acidizing by aqueous solution of acetic acid.3.Synthesis of thiazole-containing phenoxyacetic acid.The synthetic method is as follows:The 4-substituted aniline and ammonium thiocyanate were used as raw materials to form a ring under the oxidation of Br2 to give 2-amino-6-substituent benzothiazole.Then,the product was amidated with 2-hydroxy-5-substituent salicylic acid in the presence of PCl3 to abtained 5-substituted 2-hydroxy-N-(6-substituted benzo[D]thiazol-2-yl)benzamide.Finally,it reacted with ethyl bromoacetate to get produce target compounds thiazole-containing phenoxyacetic acid by nucleophilic substitution reaction.4.The bioactivities of the target compounds were tested.In growth inhibition experiment of model plants,it was found that compounds 3 and 8 showed a certain inhibitory effect on rape and barnyardgrass at high concentrations,but showed low inhibitory effects at low concentrations.The inhibitory effect of compound 3 on the root of rape was higher than that of the stem of rape.For most of the compounds,the inhibitory effect on the root of rape was beyond grade Ⅱ.For example,the inhibitory efficiency of compound 3h-2 on the root of rapeseed was 88%.A few compounds 3 had a good inhibitory effect on the stems of barnyardgrass,for example,the inhibitory effect of compound 3f-1 on the stem of barnyardgrass was 81%.Compound 8 exhibited moderate inhibitory effect on the roots of rape,and most of the inhibitory effect were between grade Ⅱ and Ⅲ.Among them,compounds 8dc and 8de had the best inhibitory effects on rapeseed root,and the inhibition rates were 78%and 74%,respectively.Compound 3 didn’t exhibite satisfactory inhibition activity for AtIspD,which indicated weak inhibitory effect of compounds 3 on IspD enzyme.Most compound 3 showed inhibitory activity toword plasmodium Dd2,indicating a broad spectrum of bioactivity of compound 3.