Synthesis Of New Spirooxindole Heterocyclic Via Multicomponent Reactions

Multicomponent reactions（MCRs）,with their advantages of simplicity and economy,especially complicated and diverse compounds can be obtained in just one reaction.Its large-scale optimization and screening of compounds with biological and pharmaceutical activity,widely attracts researcher’s attention.The spiroindole heterocyclic scaffold is found in many natural product molecules and exhibit such excellent biological activity as anti-tumor,antibacterial,and antiviral features.Due to the special structure of spiroindole skeleton,the construction of spirodindole-containing compounds is a hotspot in relevant investigates.This research,with isatinte,malononitrile and tramic acid which has a variety of biological activities as substrates,synthesized 42 indole-spiro-dihydropyridines that have not been reported in the literatures using one-pot multi-component reaction synthesis.The bioactivities of some of the compounds as well as the structure-activity relationship was investigated.The process mainly serves the research in three sections:1)Diethyl malonate and L-alanine ethyl ester hydrochloride were used to synthesize（S）-5-methytetramic acid.Subsequent reactions with different anilines successfully produced six chiral tetramic acid dilute amine compounds,and a single crystal structure of the compound 1f was obtained.2)42 unrecorded indole-spiro-dihydropyridine compounds were synthesized using chiral tetramic acid dilute amine compounds in place of isatin and malononitrile as substrates via a one-pot three-component reaction.The reaction could be easily performed in ethanol with 4-DMAP as catalyst.3)The in vitro anti-tumor activities of some synthesized compounds against Raji cells were evaluated.The result indicated that most of the compounds possessed potent inhibitory activity.The anti-tumor activity proved best(IC₅₀=18.90μM),and comparable to the inhibitory activity of the cisplatin as a positive control particularly when the 5-position on the indole ring was substituted by bromine.Figure 54;Table 11;Reference 66...