Asymmetric Synthesis And Anticancer Activity Evaluation Of Tetrahedron-?-carbolines Derivatives

As an important natural product,alkaloids are numerous,have complex structures such as nitrogen-or oxygen-containing heterocycle.Most alkaloids have significant physiological activity and meet the design requirements of"privileged structure"of modern medicinal chemistry,and gradually become the research focus,in recent years.Tetrahydro-?-carboline compounds are important components of alkaloids,which have a variety of significant pharmacological activity.On the basis of the physiological activity of carboline alkaloids and the"privileged structure"the related study was carried out in this paper,which consists of four chapters.?1?In chapter one,the progress of the asymmteric Pictet-Spengler reaction in recent 30 years was reviewed.Various asymmetric catalysis systems are classified and summarized in detail,and the possible future research directions are proposed.The chapter two could be divided into three aspects:?a?Application of quinidine based catalysts in the asymmetric Pictet-Spengler reaction to prepare tetrahydro-?-carboline derivatives.?b?Speculated the possible reaction mechanism of the reaction and validated by DFT.?c?Summarized and discussed the reaction results.The synthesized compounds were characterized by¹H-NMR,¹³C-NMR and MS.?2?Due to its rigid structure,the spirocyclic structure of alkaloids show special physiological activity in medicinal chemistry and become the new direction of medicinal chemistry.In chapter three the representativepreparationsofspirocycliccompoundsor tetrahydro-?-spirooxindines were reviewed firstly.On the basis of asymmetric Pictet-Spengler reaction catalyzed by quinidines,various tetrahydro-?-spirooxindine compounds were synthesized.Discussed the results of the experiments.The synthesized compounds were characterized by ¹H-NMR,¹³C-NMR and MS.?3?In chapter four the obtained compounds were tested for their activity by MTT assay,and the precursors compounds were screened through activity test on human lung cancer cell line A549,human liver cell line Hep G2,human colon cancer cell line HCT116 and normal hamster lung cell CHL.According to the structure and the previous literature,the possible drug target was determined.Molecular docking of the compound was carried out by the Discovery studio software to determine the active pocket.Further research will be continue.