Insecticidal activities of chiral N-trifluoroacetyl sulfilimines as potential ryanodine receptor modulators.

This is the first report of novel chiral N-trifluoroacetyl sulfilimines during research for new environmentally benign and ecologically safe novel insecticides with new modes of action. Four series of phthalamides containing 20 new structures were designed, synthesized, and evaluated against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for their insecticidal activities. The target compounds were established by corresponding (1)H NMR, HRMS (or elemental analysis), X-ray diffraction analysis, and optical polarimetry. Introduction of chiral N-trifluoroacetyl sulfiliminyl moieties into the new scaffolds showed that some target compounds possessed impressive activities as commercial flubendiamide. These N-trifluoroacetyl sulfilimines exhibited the sequence of activity against oriental armyworm as (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Rs) > (Rc, Ss), in which the chiral carbon influenced the activities stronger than sulfur. For diamondback moth, compounds If, IIa, and IIc exhibited even stronger activity than flubendiamide; especially If displayed a death rate of 100% at 10(-6) mg L(-1), much better than that of flubendiamide (0% at 10(-4) mg L(-1)). Comparative molecular field analysis calculation indicated that stereoisomers with Sc configurations containing more electronegative group as COCF3 are favorable to the insecticidal activity. The present work demonstrated that chiral N-trifluoroacetyl sulfilimines can be considered as potential insect ryanodine receptor modulators. From the standpoint of molecular design, it was concluded that the conventional second methyl group in the aliphatic amido side chain of dicarboxamide might not be a requisite in our research on novel sulfiliminyl insecticides.

Novel phthalamides containing sulfiliminyl moieties and derivatives as potential ryanodine receptor modulators.

To tackle the serious challenge of insect resistance and stricter environmental regulations, innovating a new eco-friendly insecticide is urgently required. A series of new phthalamides containing sulfiliminyl and sulfoximinyl moieties were designed and synthesized. In total, 30 new structures were characterized by 1H NMR spectra and HRMS. The bioassay results indicated that some title compounds exhibited excellent insecticidal activities against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)). 4a showed the same larvicidal level as that of commercial flubendiamide as a control. 7a and 9a exhibited outstanding activity against diamondback moth. The LC50 values of 7a and 9a were 8.33 × 10(−8) and 2.34 × 10(−8) mg L(−1), respectively, lower than that of flubendiamide (1.25 × 10(−7) mg L(−1)). The effects of 4a, 7a and 9a on intracellular calcium of neurons from the beet armyworm (Spodoptera exigua) indicated that these title compounds activate the receptor-operated calcium channel. The calcium ions efflux from the calcium store on endoplasmic reticulum (ER) when treated with novel compounds. The results of CoMFA calculation showed that N-cyanosulfilimines and N-trifluoroacetylsulfoximines might be of importance to the larvicidal activity. The present work demonstrated that structures containing sulfiliminyl and sulfoximinyl moieties can be considered as lead compounds for the development of new insect ryanodine receptor modulators.

Chiral dicarboxamide scaffolds containing a sulfiliminyl moiety as potential ryanodine receptor activators.

To search for new environmentally benign insecticides with high activity, low toxicity, and low residue, novel chiral configurations introduced into dicarboxamide scaffolds containing N-cyano sulfiliminyl moieties were first studied. Four series of phthalamides with sulfur-containing side chains were designed, synthesized, and evaluated against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for their insecticidal activities. All structures were characterized by (1)H NMR, (13)C NMR, and HRMS (or elemental analysis), and their configurations were confirmed by optical polarimetry. The biological assessment indicated that some title compounds exhibited significant insecticidal activities. For oriental armyworm, these stereoisomers exerted different impacts on biological activity following the sequence (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Ss) > (Rc, Rs), and carbon chirality influenced the activities more strongly than sulfur. Compounds Ia and IIa reached as high an activity as commercial flubendiamide, with LC50 values of 0.0504 and 0.0699 mg L(-1), respectively, lower than that of flubendiamide (0.1230 mg L(-1)). For diamondback moth, the sequence of activity was (Sc, Ss) > (Sc, Rs), and the sulfur chirality influenced the activities more greatly than carbon. Compound IIe exhibited even higher activity than flubendiamide, whereas Ie and Ic,d reached the activity of the latter. The results indicated that the improvement of insecticidal activity probably required a coordination of both carbon and sulfur chirality. Comparative molecular field analysis calculation indicated that stereoisomers with Sc configurations containing strong electron-withdrawing groups such as as CN are important in maintaining the high activity. The chiral scaffolds containing the N-cyano sulfiliminyl moiety are also essential for high larvicidal activity. Some title compounds could be considered as potential candidates for ryanodine receptor activators.