Oxidation Of Indole And Cinnamicaldehyde Compounds The Asymmetric Michael Addition Of Product Research And Its Active Evaluation

According to the principle of active skeleton splicing and migration of drug design,the splicing of two or more bioactive skeletons into a potentially biologically active multi-skeletal molecule is an extremely important research field in organic chemistry and medicinal chemistry.（1）The ketone skeleton is also ubiquitous in natural products and drug molecules.For example,the natural product molecules Ergochrome DD,Diversonol,Desoxydiversonol,Applanatin B and Isocochlioquinone A share a ketone molecule,which plays a major role in relieving pain and economic development.（2）The oxindole derivative has broad biological activity and has antitumor,antimalarial,antidepressant,antibacterial,anti-inflammatory,anti-diabetic and the like activities.Among them,anti-tumor activity is particularly prominent.Pharmaceutical chemists have been working hard to find new anti-cancer drugs with high efficiency and low toxicity.Because 3-spiroxidated indole and Indole3-quaternary carbon oxidation have their unique biological activities,and special the spatial structure has made it a potential drug molecule that has always attracted people’s attention.（3）Cinnamaldehyde（CA）,also known as cinnamaldehyde orβ-phenylacrolein,is an active compound isolated from the bark of Cinnamon plant,which has anti-diabetic,anti-obesity,antibacterial and anti-tumor activities.In thesis,two bioactive skeletons were spliced into a compound,and structural modification and modification were carried out to synthesize a series of 3-quaternary carbon oxidation skeleton derivatives,in order to find new drug candidate compounds with better activity.Therefore,the synthesis of the target product designed by this subject,as well as its structural modification and anti-tumor activity research,may have important significance in the field of medicine.Starting from oxindole and cinnamaldehyde,the target product was obtained by asymmetric Michael addition reaction,and its anti-tumor activity was studied in vitro,in order to obtain a compound molecule with better activity.The initial substrate was obtained by Aldol reaction,acylation reaction and hydrogen palladium carbon reduction,and 18 target compounds were obtained by asymmetric Micheal addition.In addition,the reaction time,catalyst,solvent,temperature,and acid-base conditions are screened to obtain an optimal reaction route with an enantioselectivity of over 90%.The route conditions were mild and simple,and a total of 18 compounds were synthesized by this route.Using MTT assay and cisplatin as positive control,the antitumor activity of 6compounds was studied in vitro,to investigate their effects on human prostate cancer cell pc-3,human non-small cell lung cancer cell A549 and human chronic myeloid leukemia cell K562.The in vitro anti-tumor activity data showed that the compounds designed in this study had certain anti-tumor activity against the three cell lines,and the K562 was more active.Some of the compounds were able to achieve the same anti-tumor activity as the positive control cisplatin,compound 3bc(IC₅₀=16.97μM),3cd(IC₅₀=16.44μM),and the positive control cisplatin(IC₅₀=25.20μM).