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林产化学与工业

林产化学与工业 ›› 2023, Vol. 43 ›› Issue (1): 43-50.doi: 10.3969/j.issn.0253-2417.2023.01.005

• 研究报告 • 上一篇    下一篇

氨基甲酸酯类化合物的合成及其AChE抑制活性研究

王婧1,2,3, 陈玉湘1,3, 李胜男1, 张红梅1,2, 蒋建新2, 赵振东1,*()   

  1. 1. 中国林业科学研究院 林产化学工业研究所；江苏省生物质能源与材料重点实验室；国家林业和草原局林产化学工程重点实验室；林木生物质低碳高效利用国家工程研究中心；江苏省林业资源高效加工利用协同创新中心，江苏 南京 210042
    2. 北京林业大学 材料科学与技术学院，北京 100083
    3. 中国林业科学研究院 林业新技术研究所，北京 100091
  • 收稿日期:2021-11-03 出版日期:2023-02-28 发布日期:2023-02-28
  • 通讯作者: 赵振东 E-mail:zdzhao@189.cn
  • 作者简介:赵振东，研究员，博士，博士生导师，主要从事萜类化学利用研究工作；E-mail: zdzhao@189.cn
    王婧(1983—)，女，山西临县人，助理研究员，博士生，主要从事萜类化学利用研究工作
  • 基金资助:
    国家自然科学基金面上项目(31870557)

Synthesis of Carbamates and Their AChE Inhibitory Activity

Jing WANG1,2,3, Yuxiang CHEN1,3, Shengnan LI1, Hongmei ZHANG1,2, Jianxin JIANG2, Zhendong ZHAO1,*()   

  1. 1. Institute of Chemical Industry of Forest Products, CAF; Key Lab. of Biomass Energy and Material, Jiangsu Province; Key Lab. of Chemical Engineering of Forest Products, National Forestry and Grassland Administration; National Engineering Research Center of Low-Carbon Processing and Utilization of Forest Biomass; Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing 210042, China
    2. College of Materials Science and Technology, Beijing Forestry University, Beijing 100083, China
    3. Research Institute of Forestry New Technology, CAF, Beijing 100091, China
  • Received:2021-11-03 Online:2023-02-28 Published:2023-02-28
  • Contact: Zhendong ZHAO E-mail:zdzhao@189.cn

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摘要：

以松节油主要组分3-蒈烯为原料首先合成了3-异丙基-5-甲酚(1)和香芹酚(2)，从这2个化合物出发通过异氰酸酯法(方法A)和氨基甲酰氯法(方法B)进一步制备了14个含异丙基甲酚结构的氨基甲酸酯类化合物，并测定了所合成16个化合物对乙酰胆碱脂酶(AChE)的抑制活性。研究结果表明：酚类化合物与异氰酸酯反应是制备氨基甲酸酯的高效合成工艺，其中异氰酸酯中N-取代基结构越大反应越容易发生，芳基取代产物的摩尔得率可达90%以上。在AChE抑制活性方面，3-异丙基-5-甲酚衍生物的抑制活性普遍高于香芹酚衍生物，N-脂基取代产物的抑制活性显著高于N-芳基取代产物，且短链脂基取代产物的抑制活性高于长链脂基和环脂基。3-异丙基-5-甲酚的N-甲基取代产物表现出优良的AChE抑制活性，抑制效率达到石杉碱甲的90.5%，超过同为氨基甲酸酯阳性对照利凡斯的明(89.6%)，而其N, N-二甲基取代产物的抑制活性又明显高于N-甲基取代产物，抑制效率达到石杉碱甲的97.9%。浓度与抑制率关系表明：3-异丙基-5-甲基苯基-N, N-二甲基氨基甲酸酯(Ⅰ-2)在浓度大于1.25 mmol/L后表现出与石杉碱甲基本等同的AChE抑制活性，具有开发为阿尔兹海默症治疗药物或者杀虫剂的潜力。

关键词: 松节油, 3-蒈烯, 氨基甲酸酯, 乙酰胆碱酯酶抑制剂, 3-异丙基-5-甲基苯基-N, N-二甲基氨基甲酸酯

Abstract:

Using 3-carene, a major component of turpentine, as the raw material, 3-isopropyl-5-cresol(1) and carvacrol(2) were first synthesized, and then 14 carbamate compounds containing isopropyl cresol structure were further prepared by their reactions with isocyanates(method A) or carbamoyl chlorides(method B). The acetylcholinesterase(AChE) inhibitory activities for all synthetic compounds were studied. The research results showed that the reaction of phenolic compounds with isocyanates was an efficient synthesis process for the preparation of carbamates. The larger N-substituent structure in the isocyanate, the easier reaction occurs, and the molar yield of aryl substitution products could reach more than 90%. In terms of AChE inhibition, the activities of 3-isopropyl-5-cresol derivatives were generally higher than those of carvacrol derivatives. The activities of N-aliphatic substituted products were significantly higher than those of N-aryl substituted products, and the activities of short-chain aliphatic substituted products were higher than those of long-chain aliphatic and cycloaliphatic groups substituted products. The N-methyl substituted product of 3-isopropyl-5-cresol showed the excellent AChE inhibitory activity of 90.5% against Huperzine A and surpassed the positive control Listigmine(89.6%), which was a commercial AChE inhibitor with carbamate. The activity of N, N-dimethyl substituted product of 3-isopropyl-5-cresol was evidently higher than its N-methyl substituted product, whose inhibition efficiency reached 97.9% of Huperzine A. The relationship between the concentration and the inhibition rate showed that 3-isopropyl-5-methylphenyl-N, N-dimethylcarbamate(Ⅰ-2) had a substantially equivalent AChE inhibitory activity to Huperzine A when the concentration was greater than 1.25 mmol/L, indicating that it had the potential to be developed as a therapeutic drug for Alzheimer's disease or insecticide.

Key words: turpentine, 3-carene, carbamate, acetylcholinesterase inhibitor, 3-isopropyl-5-methylphenyl-N, N-dimethylcarbamate

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