Studies On The Synthesis And Activity Of Scrodentoids A And The Construction Of Anthrone And Carbazole Compounds

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,the therapeutic material basis of TCM contains abundant biologically active molecules.In-depth research on the effective ingredients of TCM can clarify the therapeutic material basis of TCM.This is an effective method to solve key scientific problems in the application of TCM,a great source for new drug and one of the important ways for innovating TCM.The dissertation is based on development of bioactive constituents of single herb,which mainly includes three parts:(1)Study on synthesis and anti-allergy activity for Scrodentoid A in TCM.(2)Study on construction of anthrone skeleton.(3)Study on construction of carbazole skeleton.The synthesis and anti-allergy of Scrodentoid A,the bioactive molecule in TCM,were studied in the first part.Scrodentoid A is a natural anti-allergy bioactive Chinese herb extracted from the Scrophularia dentata Royle ex Benth.The natural chiral source dehydroabietic acid was used as the starting materials,the synthesis whole route was 11 steps,and the total yield was 9%.In the synthesis process,the one-step construction of ortho hydroxyl group of aromatic isopropyl group was realized by the oxidative hydroxylation reaction and the construction of the terminal double bond was realized by the oxidative decarboxylation.In addition,16 analogues were synthesized through structural modification of Scrodentoid A,of which 5 compounds have high anti-allergic activity,and the concentration-dependent studies showed that these 5 compounds were all concentration-dependent.The second part is the skeleton construction of anthrone compounds,which are bioactive molecules of TCM.We developed a new synthetic method through metal catalytic to construction the skeleton of anthrone compounds.The method has a wide range of substrate applicability,and can be used for a variety of strong electron-withdrawing and large sterically hindered substrates.The structure of product was confirmed by X-ray single crystal diffractive,the hydrogen atoms loss in the reaction were detected by mass spectrometry in the form of hydrogen.In addition,we speculated the reaction mechanism and proposed two reaction paths.At the same time,we did some transformation experiments on the synthesized products,which will provide a methodological reference for the future synthesis of anthrone compounds,which are bioactive molecules of TCM.The third part is the construction of carbazole skeleton.Carbazole compound are bioactive molecules in TCM.The bromobenzene and 2-phenylindole were cross-coupled to efficiently synthesize compounds with carbazole basic skeleton by palladium-catalyzed reaction.This process realized the activation of three C-H bonds and the construction of two C-C bonds in one step.The reaction showed higher efficiency and mild reaction conditions,and provided a convenient synthetic method for the subsequent synthesis of carbazole compounds,which are active molecules of TCM.