Study On Synthesis And Antitumor Activity Of N,S Polysubstituted Trans-stilbene Derivatives

Stilbene is a class of compounds with diphenylethene as parent nucleus,which have extensive physiological activities.In recent years,the researches on stilbenes have been developing rapidly.Because natural stilbene ingredients have limited resources and low content,using organic synthetic methods to obtain a variety of stilbene derivatives have become the important solution to the shortage of natural source.Furthermore,the activities of stilbene compounds can be enhanced by changing the substituent groups of the structure.Overall,traditional synthesis method is to link two modified aromatic rings,and then form the structure of stilbene.In this paper,the researches on totally new synthesis methods from the view of constructing aromatic rings have been studied.On the basis of domestic and overseas studies on a-oxoketene-(S,S)-acetals,a totally new synthesis route of stilbene derivatives via[5+1]annulation was developed.By this route,a series of new stilbene derivatives attached with N,S,hydroxyl,methoxy,alkyl and amide groups were obtained.The contents and results of this study are mainly as follows:A new synthetic route for stilbene derivatives was developed.It mainly includes three steps.Firstly,the non ring intermediate ?a-oxoketene-(S,S)-acetals was synthesized.Using the method of "one pot" to combine the synthesis of acetoacetamide and construction in one step reaction,then produced 7 compounds.Secondly,the former obtained intermediate was reacted with cinnamaldehyde by the method of Claisen condensation,and produced 12 intermediates of a-alkenoyl ketene-(S,S)-acetals.Finally,the key step[5+1]annulation reaction,?-alkenoyl ketene-(S,S)-acetals and nitroparaffin were used as 5C and 1C synthons respectively and 12 new stilbene derivatives were obtained via annulation reaction.All the products were identified by MS,1H-NMR and 13C-NMR.Antitumor activities in vitro of 12 synthetic stilbene derivatives were assessed by MTT method.The inhibition rates of three kinds of cancer cells,including human breast cancer cell line MCF-7,human liver cancer cell lines HepG-2 and human gastric cancer cell line SGC-7901,were determined in the experiments.The results show that the new derivatives of 3d,3j and 3m have obvious antitumor activity,with IC50 values below those of the control resveratrol.The IC50 values of derivative 3d towards MCF-7 and SGC-7901 were 55.51 ?M and 33.54 ?M,respectively;The IC50 values of derivative 3j towards HepG-2 was 11.92 ?M;The IC50 values of derivative 3m towards MCF-7,HepG-2 and SGC-7901 were 38.69 ?M,19.34 ?M and 38.80?M,respectively.In this paper,a total of 31 new compounds have been synthetized,19 of which are new derivatives intermediates,and 12 of which are new stilbenes with polysubstituted groups.Thus,the paper provides an important scientific research foundation for the synthesis of stilbene compounds and their antitumor activities.