Chinese Journal of Organic Chemistry >
Studies on the Synthesis, Structural Characterization and Biological Activities of Novel Caffeine Derivatives Containing Substituted-Piperazine Moiety
Received date: 2021-05-11
Revised date: 2021-06-23
Online published: 2021-07-13
Supported by
National Natural Science Foundation of China(21772103); National Natural Science Foundation of China(22077070)
Based on a strategy of introducing the “piperazine” bioactive group into 8-position of caffeine, sixteen novel caffeine derivatives containing substituted-piperazine moiety (Ia~Ip) have been synthesized using 8-chlorotheophylline and substituted-piperazine as materials, via multi step reactions of N-methylation, nucleophilic substitution, (protection)deprotection, etc. The structures of the title compounds were confirmed and characterized by melting point, 1H NMR, 13C NMR, and HRMS. The single-crystal structure of 8-(4-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl)piperazin- 1-yl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (Ip) was obtained. The bioassay results showed that most of the title compounds possess good insecticidal activities against Plutella xylostella L. and Mythimna separata Walker. In particular, some of the compounds exhibited better larvicidal effect towards Plutella xylostella L. than that of control caffeine, among which 8-(4-(4-fluorophenyl)piperazin-1-yl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (Ie) and 1,3,7-trimethyl-8-(4-(4- nitrobenzoyl)piperazin-1-yl)-3,7-dihydro-1H-purine-2,6-dione (In) at a test concentration of 100 mg•L–1 held lethality rate of 60% and 53%, respectively. In addition, partial compounds at 50 mg•L–1 concentration possessed >50% fungicidal activities against Physalospora piricola, Rhizoctonia cerealis, Sclerotinia sclerotiorum, etc. The research results in this paper provide useful reference for further design of novel agrochemicals based on the natural product structure of xanthine.
Key words： xanthine; caffeine; piperazine; synthesis; insecticidal activity; fungicidal activity
Shuyun Zhang , Hang Liu , Lei Wang , Zhengming Li , Baolei Wang . Studies on the Synthesis, Structural Characterization and Biological Activities of Novel Caffeine Derivatives Containing Substituted-Piperazine Moiety[J]. Chinese Journal of Organic Chemistry, 2021 , 41(10) : 4075 -4082 . DOI: 10.6023/cjoc202105020
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