Synthesis and evaluation of novel xanthine-acrylamides and xanthine-acrylates as insecticidal agents.

Abstract

The design and discovery of novel pesticidal agents according to bioactive natural products is an important aspect of agrochemical innovation. New xanthine derivatives derived from natural xanthine or methylxanthines are rich resources that possess great potential to afford new active pesticidal molecules. Herein novel xanthine derivatives were designed through a strategy of combining the methylxanthine caffeine skeleton with the acrylamide or acrylate motif of cinnamic acid derivatives. A series of novel (E)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)acrylic acid derivatives, caffeine-(E)-acrylamides and caffeine-(E)-acrylates, were synthesized and confirmed via melting points, 1 H NMR, 13 C NMR and high-resolution mass spectrometry. A single crystal of compound I12 was obtained to illustrate the trans-configuration of the vinyl double bond. Preliminary insecticidal evaluations showed that some of the compounds had favorable insecticidal potentials against Mythimna separata Walker at 200 mg L-1 . Some of the compounds exhibited excellent insecticidal activity against Plutella xylostella L. at low test concentrations, e.g. I18 and I24 with LC50 values of 0.0435 and 0.0133 mg L-1 , respectively, were found to be more potent than the insecticide control triflumuron. The structure-activity relationship (SAR) analysis is also given in detail. Compounds I12, I18, I24 and I26 generated from the integration of natural methylxanthine (caffeine) and acrylate moieties could be novel insecticidal leading compounds for further structural optimization. The SAR analysis may bring a new inspiration to the extensive and deep investigations on new xanthine derivatives in the agrochemical area.