Design, Synthesis, and Bioactivity Study of α-Thiocyanato-Substituted Spirocyclic Tetramic Acid Derivatives.

Abstract

To develop structurally novel spirocyclic tetramic acid insecticides and acaricides with high activity and low toxicity, a rational molecular modification was implemented by introducing a thiocyanato (SCN) group at the α-position of the spirocyclic tetramic acid bioactive intermediates. These new α-SCN-substituted tetramic acid derivatives were synthesized through an electrophilic thiocyanation reaction. Bioassays revealed that compounds C16 (LC50 = 0.379 mg/L) and C20 (LC50 = 0.410 mg/L) exhibited superior acaricidal activity against Tetranychus cinnabarinus compared to spirodiclofen (LC50 = 0.520 mg/L). Compound C1 exhibited insecticidal activity against Aphis craccivora (LC50 = 0.663 mg/L), which was similar to that of spirotetramat (LC50 = 0.503 mg/L). Compounds C16 and C28 displayed remarkable herbicidal activity at 500 g ai/ha against gramineous weeds (such as Digitaria sanguinalis, Echinochloa crusgalli, and Leptochloa chinensis) with broad-spectrum weed control potential. Embryotoxicity assessment in zebrafish (Danio rerio) indicated significantly reduced developmental toxicities for C1 (LC50 = 13.1 mg/L) and C16 (LC50 = 6.86 mg/L) compared to those for spirotetramat (LC50 = 2.73 mg/L) and spirodiclofen (LC50 = 0.334 mg/L). Systemic translocation bioassay demonstrated that highly bioactive compounds C1 and C16 have systemic translocation similar to that of spirotetramat. This study successfully developed a series of spirocyclic tetramic acid derivatives with high bioactivity and lower aquatic toxicity through the rational incorporation of the SCN group. The findings provide a valuable approach for the innovation of environmentally friendly pesticide molecules.