Design, Synthesis, and Safener Activity of Novel Methyl (R)-N-Benzoyl/Dichloroacetyl-Thiazolidine-4-Carboxylates

Abstract

A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates were designed by active substructure combination. The title compounds were synthesized using a one-pot route from l-cysteine methyl ester hydrochloride, acyl chloride, and ketones. All compounds were characterized by IR, 1H NMR, 13C NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The biological tests showed that the title compounds protected maize from chlorimuron-ethyl injury to some extent. The ALS activity assay showed that the title compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl. Molecular docking modeling demonstrated that Compound 4e competed against chlorimuron-ethyl to combine with the herbicide target enzyme active site, causing the herbicide to be ineffective.

Herbicide Safeners: From Molecular Structure Design to Safener Activity

“…Compound 3 competed with clorimuron-ethyl at the target active site by preventing the herbicide from acting on the ALS active pocket, thereby causing clorimuron-ethyl to lose its action. The ALS enzyme activity test results also showed that compound 3 almost reversed clorimuron-ethyl-triggered inhibition …”

“…Chlorimuron-ethyl, an ALS inhibitor, suppresses branched chain amino acid synthesis by preventing isoleucine, leucine, and valine syntheses, ultimately causing weed death . However, chlorimuron-ethyl causes injury to legumes, and its residues may inhibit the growth of subsequent crops such as maize. , Through active substructure splicing, a series of novel methyl (R)- N -benzoyl/dichloroacetyl-thiazolidine-4-carboxylates was designed and synthesized . Bioactivity tests showed that the target compounds exhibited some protection against chlorimuron-ethyl damage on maize (Figure b).…”

Research Progress in the Design and Synthesis of Herbicide Safeners: A Review

“…R-28725 [2,2-dichloro-1-(2,2-dimethyloxazolidin-3-yl)­ethan-1-one] was a mature safener with good biological activity, and thiazolidines are thought to have similar chemical properties to R-28725 as a result of bioisosterism. , Zhao et al designed and synthesized a series of thiazolidine-4-carboxylates bound by different groups at the N-3 position, retaining the thiazolidine ring as the parent skeleton structure (Scheme ) based on active substructure splicing and bioisosterism. The compounds were shown to have certain safener activities in maize and increased the ALS enzyme activity.…”

Safening activity and metabolism of the safener cyprosulfamide in maize and wheat

“…16 Directed synthesis studies have shown that subtle modifications to the structure of CSA can affect its bioactivity, identifying the retention of the cyclopropyl group as a chemical feature required for its safener activity. 17,18 Therefore, one explanation for CSA's species specificity is that this safener is metabolised to different derivatives that vary in their protective activity in different crops. To evaluate this hypothesis, we now report on the activity and associated metabolism of CSA in safener-responsive maize and nonresponsive wheat.…”