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Synthesis of 9-Substituted Berberine Derivatives with Microwave Irradiation

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Chemical Research in Chinese Universities Aims and scope

Abstract

Hyperglycemia is frequently accompanying with hyperlipidemia. To explore the potent drugs with dual-activity and dual-site effects that could reduce blood glucose and blood lipid at the same time, fibrate group with lipid-lowering effect on the 9th position of berberine(BBR) was introduced using the drug design combination principle and the multitarget collaborative treatment method. Moreover, the molecular structure of BBR was modified, and six 9-substituted derivatives of BBR were designed and synthesized, among which, five compounds have never been reported before. In addition, the molecular structures of these derivatives were identified using liquid chromatography-mass spectrometry(LC-MS), 1H nuclear magnetic resonance(1H NMR) and 13C NMR, respectively. Furthermore, the microwave irradiation experimental technique was applied in the synthesis reaction using the novel microwave synthesizer, which accelerated the reaction rate, enhanced the reaction yield, reduced the reaction by-products, and simplified the post-processing steps. In the meantime, the 9-position regioselective demethylation of BBR was explored through quantum chemical calculation during the synthesis of berberrubine. The computations were consistent with the experimental results, which contributed to deducing the mechanism of its selective methylation.

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Authors and Affiliations

  1. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, 430000, P. R. China

    Xie Han & Wenxiang Hu

  2. Jingdong Xianghu Microwave Chemistry Union Laboratory, Beijing Excalibur Space Military Academy of Medical Sciences, Beijing, 101601, P. R. China

    Xie Han, Kaiyuan Shao & Wenxiang Hu

  3. Space Systems Division, Strategic Support Troops, Chinese People’s Liberation Army, Beijing, 100101, P. R. China

    Wenxiang Hu

Authors
  1. Xie Han
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  2. Kaiyuan Shao
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  3. Wenxiang Hu
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Correspondence to Wenxiang Hu.

Additional information

Supported by the National Science and Technology Innovation Fund of China(No.09C26211100074) and the Beijing Municipal Government Special Fund, China(No.009-0753003).

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Han, X., Shao, K. & Hu, W. Synthesis of 9-Substituted Berberine Derivatives with Microwave Irradiation. Chem. Res. Chin. Univ. 34, 571–577 (2018). https://doi.org/10.1007/s40242-018-7425-6

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  • DOI: https://doi.org/10.1007/s40242-018-7425-6

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