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    Home > Biochemistry News > Biotechnology News > Important progress has been made in the synthesis of novel sesquiterpene dimers in Artemisia plants where Kunming plants are located

    Important progress has been made in the synthesis of novel sesquiterpene dimers in Artemisia plants where Kunming plants are located

    • Last Update: 2022-01-09
    • Source: Internet
    • Author: User
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      The unique structure of natural products is an important source of biologically active substances and drug discovery.
    Among
    the small molecule anti-tumor drugs approved for marketing from 1981 to 2019 , natural products directly become new drugs accounted for 9.
    7%
    , and natural product derivatives accounted for 23.
    2%

    .
    Sesquiterpenoids are widely found in plants, fungi, bacteria and insects, and their structures are diverse and their activities are remarkable.
    Especially their anti-tumor activity has attracted wide attention from medicinal chemists

    .
    Sesquiterpene
    derivatives such as agrabin, mirin, artemisinin, etc.
    have been developed as anti-tumor drugs or are in clinical research
    .
    Sesquiterpene dimer is
    a kind of complex natural product with 30 carbon atom skeleton connected by two sesquiterpene units .
    A large number of proteins responsible for cell functions in life exist in the form of dimers or need to be activated by dimerization before mediating certain signaling pathways.
    At the same time, targeting the two monomers of dimer proteins is an important part of drug research.
    Strategy
    .
    Since the sesquiterpene dimer has the potential to act on the two monomers of the dimer protein at the same time, the sesquiterpene dimer usually has better biological activity than its monomer compound .



      The Chen Jijun research team at the Kunming Institute of Botany, Chinese Academy of Sciences is committed to finding anti-hepatocarcinoma lead compounds and innovative drugs from Artemisia plants with unique structures and novel mechanisms of action
    .
    Guided by anti-liver cancer activity and guided by
     LC-MS  analysis, the research team
    conducted a preliminary study on the anti-liver cancer active ingredients of Artemisia sphaerocephala isolated and identified 143 compounds from it, and found 41 sesquiterpene dimers ( Ata Pharmaceutica Sinica B)  , 2021 , 11, 1648–1666 Organic Chemistry Frontiers 2021 , 8, 1249–1256 ; Chinese Journal of Chemistry ; 2021 , doi:10.
    1002/cjoc.
    202100528
    ) .
    The discovered sesquiterpene dimers are mainly polymerized by intermolecular Diels-Alder reaction, including 8 types of polymerization , and their anti-liver cancer activity is more significant than that of monomer compounds .
    Especially a
     

    The four compounds of rtematrolides A, J, K  and lavandiolide  are more active than the positive drug sorafenib
    .
    Mechanism studies have shown that dimers can induce apoptosis in a dose-dependent manner, down
    - regulate the expression of Bcl-2 , and activate PARP-1 to up - regulate the expression of PARP-1 .
    However, due to the low content of dimer in plants, the structure-activity relationship and target of anti-liver cancer activity are unknown, which restricts its in-depth research, development and utilization .


     

      The biomimetic synthesis of dimers based on high content of sesquiterpenes can not only verify the biogenic pathway of the compound, and quickly obtain the target compound, but also provide a synthetic route for the synthesis of analogs and lay the foundation for the structure-activity relationship study
    .
    Recently, the research team
    established a key method for the efficient synthesis of sesquiterpene dimers based on the analysis of the biogenic synthesis pathways of dimers, using arglabin , which has a higher content in Artemisia plants , as a substrate : ( 1)  Through trivalent titanium The promoted epoxy isomerization reaction constructs the diene in one step; ( 2) The dimer is obtained with high stereoselectivity through the biomimetic Diels-Alder reaction .
    Through 4-6 steps of reaction, the semi-synthesis of natural products of lavandiolides H, I, K and artematrolide F was completed with a yield of up to 60% , and the  synthesis can reach a scale of 10g , laying a material foundation for subsequent in-depth biological activity research .
    Based on the Diels-Alder reaction between the sub-divisions , the established synthetic methodology was successfully applied to " natural product-like


    " Sesquiterpene dimers, trimers efficient synthesis, the tetramer were found to have a significant cytotoxic activity against cancer, the study is based on two subsequent synthesis of highly active anti-tumor activity sesquiterpenoids compound The aggregates are provided for reference
    .
     

     

      Related research recently to "Biomimetic Synthesis of Lavandiolides H, the I, F and K and Artematrolide Via Diels  ?  Alder Reaction" in the title in Organic Letters published (magazines 2021 , 23 8380-8384 )
    .
    Dr.
    Tianze Li / Associate Researcher is the first author, and Researcher Chen Jijun is the corresponding author
    .
    This research work has won the National Natural Science Foundation of China's key project
    (22137008) , the Chinese Academy of Sciences Youth Innovation Promotion Association project (2020386), the  young and middle-aged academic and technical leaders reserve talents of Yunnan Province, and the State Key Laboratory of Phytochemistry and the Sustainable Utilization of Western Plant Resources Support for independent research topics and other projects
    .

      Article link 

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