Design, synthesis, crystal structure, bioactivity, and molecular docking studies of novel sulfonylamidine-derived neonicotinoid analogs

Abstract

Two novel series of sulfonylamidine-derived neonicotinoid analogues were designed and synthesized via a Cu-catalyzed one pot reaction. The structures of the target compounds were characterized by 1 H-NMR, 13 C-NMR, HR-MS and the single-crystal structure of 14k was further determined by X-ray diffraction crystallography. In preliminary bioassays, many of the target compounds exhibited significant activity against Tetranychus cinnabarinus (carmine spider mite) and Brevicoryne brassicae (cabbage aphid). Some structural features important for potency were observed, and a model of the ligand-receptor complex was also generated with a molecular docking study using representative active analogues. The molecular binding mode observed at the active site of the nicotinic acetylcholine receptor model should provide useful information for future structure-based design of novel sulfonylamidine-derived neonicotinoid analogues.

A holistic study of neonicotinoids neuroactive insecticides—properties, applications, occurrence, and analysis

“…In beginning of 2000s, two new neonicotinoids were introduced to the general market—clothianidin and thiamethoxam. Currently, the majority of crops (mainly corn and soy) are treated with one neonicotinoid and fungicidal products (Jeschke et al 2011; Yang et al 2014).…”

“…Neonicotinoids are hydroheterocyclic guanidines/amidines, and they posses active substituents (Fig. 3) (Yang et al 2014).

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“…The sulfonamide derivatives may show significant activity in insect and acari control, but a change of substitutes can result in great disparities in strength. Individual insecticides may vary in strength and way of action due to a combination of factors like the number of substitutions, elasticity, or participation of free electrons (Yang et al 2014).…”

“…It is useful to search continuously for new neonicotinoid compounds because it has been observed that their use too frequently in one given area, and for certain insect species, develops significant resistance. Modification of the structures of existing neonicotinoids may be an effective way of eliminating resistance in insects (Yang et al 2014). Moreover, it was concluded that any insecticide leads to insect resistance when used continuously for a long period (Pisa et al 2017).…”

Synthesis and Insecticidal Activity of Mesoionic Pyrido[1,2-α]pyrimidinone Derivatives Containing a Neonicotinoid Moiety

“…Intermediates A , B , and C were prepared according to the reported methods [ 38 , 39 , 40 , 41 , 42 , 43 ]. First, 2-chloro-5-chloromethylpyridine was slowly added to the aqueous solution of NaHCO 3 and 2-aminopyridine.…”