Green Click Synthesis And Anticancer Activity Of 4-Trifluoroacetyl Triazole Compounds

Triazole heterocyclic compounds have unique physicochemical properties and are favored in the field of medicinal chemistry.Among them,1,2,3-triazole compounds have a wide range of anti-tumor,anti-inflammatory,anti-tuberculosis（TB）,antiviral and other biological activities,which have attracted extensive attention.Metal-catalyzed click chemistry is the most important method for the synthesis of triazole,but with the improvement of people’s environmental awareness,green pharmaceutical technology has become an issue that should be concerned in the process of drug development.Therefore,it is important to find a green method without heavy metal catalysis.In this paper,we studied a green click-chemistry method without solvent or catalyst.Under this condition,the reaction of benzyl azide reacts with trifluoromethyl-α,β-alkynone to form 4-trifluoroacetyl triazole compounds has good yield and stereoselectivity.In the first part,benzyl azide derivatives and trifluoromethyl-α,β-alkynone were used to generate 4-trifluoroacetyltriazole compounds via click-chemical reaction.Conditional screening shows that the target product can be obtained with good regioselectivity at room temperature in the absence of solvent and no catalyst.Then the reaction temperature was optimized and the optimal reaction conditions were finally explored:under the condition of no solvent and no catalyst,the two reaction materials reacted for 12 hours with equivalent value at 60^oC,and 214-trifluoroacetyltriazole compounds with novel structures were obtained in the range of 80-95%yield,and their structures were confirmed by NMR and HRMS spectrum.The second part introduces the functional group conversion of the carbonyl group in the 4-trifluoroacetyl triazole derivative,which is respectively converted into the corresponding hydroxyl group（by reduction reaction）,double bond（via Witting reaction）and deuterated difluoromethylene group（Nucleophilic fluorination reaction by DAST）,and all three transformations have good substrate suitability,and a plurality of different fluorine-substituted triazole derivatives were obtained by conversion.The third part introduces the anti-tumor activity of 4-trifluoroacetyltriazole derivatives and their corresponding functional group transformants.In vitro anti-tumor activity test:the 4-trifluoroacetyltriazole compound has been tested for its anti-tumor activity against HeLa,A-549,HTC-116,HepG2,MKN45 and MGC-803tumor cells,and it has certain anticancer activity.Among them,3ba had the best anticancer activity against HepG2 cells with an IC₅₀0 of 0.0267 mmol/ml;the functional group transformants tested the effects on the anti-tumor activity of Hela,HepG2 and HL-60 tumor cells.There was a general growth-inhibiting activity against all three cancer cells,and excellent in inhibiting the growth of HL-60 cells.Among them,the inhibition rate of 5i against HL-60 cells can reach 87%,which also provides some ideas for the development of new anti-tumor drugs.