Studies On The Design,Synthesis And Safener Activity Of Substituted Ester Thiazolidanes

Herbicide safeners are a class of pesticides that can reduce the negative effects of herbicides on crops.According to our previous research on the design of nitrogen-containing heterocyclic herbicide safeners,the target compounds were designed and synthesized based on bioisosterism and active substructure combinations retaining R-28725 as the lead compound,in order to be able to protect corn from the damage by sulfonylurea herbicides.In this study,three types of compounds were synthesized.There are methyl（R）-N-benzoyl-thiazolidine-4-carboxylates,methyl（R）-N-dichloroacetylthiazolidine-4-carboxylates and methyl（R）-N-（tosylcarbamoyl）thiazolidine-4-carboxylates.L-cysteine methyl ester hydrochloride was cyclized with ketones to generate thiazolidine intermediates under basic conditions.Methyl（R）-N-（tosylcarbamoyl）thiazolidine-4-carboxylates were synthesized from thiazolidine intermediates and toluenesulfonyl isocyanate at low temperatures,with 60-93%yields.Methyl（R）-N-benzoyl-thiazolidine-4-carboxylates and methyl（R）-N-dichloroacetylthiazolidine-4-carboxylates were synthesized using a one-pot route,in a yield of 29-91%.A total of 44 compounds were designed for this project and 41 of them were successfully synthesized.All compounds were characterized by IR,¹H NMR,¹³C NMR,and HRMS.The structure of VIII and XIV was determined by X-ray crystallography.The safener activity of the compounds were determined by the bioactivity text.The residual concentration of chlorimuronethyl in soil was determined as 24μg·kg^-1.In the preliminary screening,it was found that the best growth index was obtained when controlling the concentration of methyl（R）-4-（p-nitrobenzoyl）-1-thia-4-azaspiro[4.5]decane-3-carboxylate（XII）at 25 mg·kg^-1.Maize seeds were soaked in a solution of the compounds(25 mg·kg^-1)overnight and incubated in a growing chamber for a week.The plant height,root length,plant fresh weight,root fresh weight and enzyme activity of maize was determined to investigate the safener activity of the target compounds.The results showed that most of the compounds had different degrees of protection effect on maize,and the safener activity of methyl（R）-4-（o-methoxybenzoyl）-1-thia-4-azaspiro[4.5]decane-3-carboxylate（XV）was better than R-28725.Enzymatic activity tests showed that the safener achieved detoxification effect by enhancing GST,ALS activity and GSH concentration.Molecular docking indicated that the safener increased target enzyme activity by competing with the herbicide for target sites.Comparing the recovery rate of the target compounds showed that substituents played a key role in the safener activity.In general,spiro compounds had higher activity than other compounds and methyl（R）-N-（tosylcarbamoyl）thiazolidine-4-carboxylates were less active than methyl（R）-N-benzoylthiazolidine-4-carboxylates.For methyl（R）-N-benzoyl-thiazolidine-4-carboxylates and methyl （R）-N-dichloroacetylthiazolidine-4-carboxylates,the target compounds with o-methoxybenzoyl and p-chlorobenzoyl would show higher safener activity than other compounds.