Chinese Journal of Organic Chemistry >
Studies on the Synthesis and Biological Activities of Novel Dihydroquinazolinone-Containing Caffeine Derivatives
Received date: 2022-06-16
Revised date: 2022-08-21
Online published: 2022-09-15
Supported by
National Natural Science Foundation of China(22077070); National Natural Science Foundation of China(21772103)
Based on the strategy of introducing the “dihydroquinazolinone” bioactive group into 8-position of caffeine, thirteen novel caffeine derivatives containing dihydroquinazolinone moiety have been synthesized using theophylline and isatoic anhydride/5-bromoisatoic anhydride as materials, via multi-step reactions such as N-methylation, palladium-catalyzed coupling, nucleophilic addition-elimination and condensation, etc. The bioassay results showed that most of the compounds possess favourable insecticidal activity against Plutella xylostella L., among which 1,3,7-trimethyl-8-(4-(4-oxo-3-propyl-1,2,3,4- tetrahydroquinazolin-2-yl)phenyl)-3,7-dihydro-1H-purine-2,6-dione (Ia) and 8-(4-(6-bromo-3-(4-fluorobenzyl)-4-oxo-1,2,3,4- tetrahydroquinazolin-2-yl)phenyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (Im) held lethality rate of 50% and 43% respectively at a test concentration of 50 mg•L–1, especially Ia still had 20% lethality rate at 10 mg•L–1. Partial compounds also showed good herbicidal activities. In particular, Ia held an growth inhibition rate of 96.6% against root of Brassica campestris L. at a test concentration of 100 mg•L–1, which was better than that of the control chlorsulfuron. In addition, partial compounds possessed >50% fungicidal activities at 50 mg•L–1 against Sclerotinia sclerotiorum, Phytophthora capsicum, Physalospora piricola, etc. The inhibitory activity of Ia against Phytophthora capsicum reached 80.6%, which greatly exceeded that of the contrast caffeine. Compounds Ia exhibited good biological activities in almost all the insecticidal, herbicidal and fungicidal bioassays, and could be considered as a novel pesticide lead compound to carry out further structural optimizations. The results of this study provide useful reference for the design of new pesticidal agents based on the structure of natural products.
Lei Wang , Shujing Yu , Na Yang , Baolei Wang . Studies on the Synthesis and Biological Activities of Novel Dihydroquinazolinone-Containing Caffeine Derivatives[J]. Chinese Journal of Organic Chemistry, 2023 , 43(1) : 299 -307 . DOI: 10.6023/cjoc202206024
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