Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (10): 4075-4082.DOI: 10.6023/cjoc202105020 Previous Articles     Next Articles

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新型含取代哌嗪的咖啡因衍生物的合成、结构表征及生物活性研究

张舒昀, 刘航, 汪蕾, 李正名, 王宝雷*()   

  1. 南开大学化学学院 元素有机化学国家重点实验室 天津 300071
  • 收稿日期:2021-05-11 修回日期:2021-06-23 发布日期:2021-07-12
  • 通讯作者: 王宝雷
  • 基金资助:
    国家自然科学基金(21772103); 国家自然科学基金(22077070)

Studies on the Synthesis, Structural Characterization and Biological Activities of Novel Caffeine Derivatives Containing Substituted-Piperazine Moiety

Shuyun Zhang, Hang Liu, Lei Wang, Zhengming Li, Baolei Wang()   

  1. State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
  • Received:2021-05-11 Revised:2021-06-23 Published:2021-07-12
  • Contact: Baolei Wang
  • 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