Oxathiazepane compounds as potential insecticidal agents

The spread of insecticide resistance among major agricultural and vector pests necessitates the discovery of compounds with novel modes of action and favorable safety profiles. 1,5,3-Oxathiazepanes represent a previously unexplored class of heterocycles. This study aimed to evaluate the insecticidal potential of ten 1,5,3-oxathiazepane derivatives and assesses their toxicity in mammals and human cells.

Screening against Drosophila melanogaster adults identified aliphatic-substituted derivatives (compounds 1-6) as active, with compounds 1-4 causing 100% mortality at 1% within 48 h. Aromatic or heteroaromatic substituents led to a complete loss of activity. Compound 3 (3-hexyl-1,5,3-oxathiazepane) showed concentration-dependent insecticidal effects, with 24 h median lethal concentration (LC₅₀) of 0.77% (7.7 g L^-1) via feeding and 24-h median lethal dose (LD₅₀) of 3.1 μg per fly via topical application. At 3% (30 g L^-1), compound 3 killed 100% of Tenebrio molitor and Oxyhaloa deusta within 24 h. Acute oral LD₅₀ in mice was 1098 mg kg^-1 (hazard category 4).

This is the first report of insecticidal activity in 1,5,3-oxathiazepanes. Compound 3 exhibits broad-spectrum activity across multiple insect orders and low mammalian toxicity, combined with a scalable one-pot synthesis. These findings establish oxathiazepanes as a new chemical scaffold with interesting insecticidal activity and a favorable safety profile against mammals, which warrants further investigation to determine its mode of action and potential for managing resistance. © 2026 Society of Chemical Industry.