Synthesis Of Spirooxindole Derivatives Via Multicomponent Reactions

Spirooxindole is the core skeleton of a large class of natural alkaloids and drug molecules.These special heterocyclic systems have highly significant biological characteristics and have become the dominant structures of candidate drugs and clinical drugs.Exploring the synthesis of these compounds is not only conducive to the development of their efficient synthesis methods,but also has important significance for the biological activity of the compounds.Multicomponent reactions?MCRs?are a synthetic method widely used in organic chemistry and pharmaceutical chemistry.The characteristic of MCRs is that the condensation products containing all the substrate core structures can be obtained through single step operation from multiple simple molecules.Excellent applicability and flexibility make it suitable for the synthesis of spirocyclic compound with various substituents and complex structures.In this paper,two MCRs for the synthesis of new spirooxindole derivatives have beendeveloped,25spiro[4H-pyran-3,3'-oxindoles]derivativesand30dispiro[benzofuran-2,2'-pyrrolizine-3',3''-oxindoles]derivatives were synthesized.The biological activity of the product was preliminarily studied.The specific contents are as follows:Part?:Iodine-promoted three-component reaction for the synthesis of spiro[4H-pyran-3,3'-oxindoles]derivatives.Under the catalysis of I₂,the spiro[4H-pyran-3,3'-oxindoles]derivatives were synthesized by a one-pot method using isatin derivatives,1,3-dicarbonyl compounds and 4-hydroxycoumarin as raw materials.We studied the effect of the amount of I₂,solvent and temperature on the yield of the reaction,and selected the optimal conditions.25 spiro[4H-pyran-3,3'-oxindoles]derivatives?TM-01^TM-25?were synthesized under optimal conditions,yields up to 91%.The structure of the products was confirmed by ¹H NMR,¹³C NMR and elemental analysis,and the molecular structure was further determined by X-ray single crystal diffraction results of TM-13 and TM-22.In addition,we propose two possible reaction mechanisms,The antibacterial activity of 13 products was tested.The preliminary results showed that most of the products had more than 50%inhibitory activity on apple ring rot and wheat sharp eyespot.The method has the advantages of readily available raw materials,high yield and simple operation,and the target compound has certain antibacterial activity.It not only provides a new synthesis method for the spirooxindole compounds,but also provides a reference for the study of biological activity.Part?:Synthesis of dispiro[benzofuran-2,2'-pyrrolizine-3',3''-oxindoles]derivatives by Multicomponent reactions.Dispiro[benzofuran-2,2'-pyrrolizine-3',3''-oxindoles]derivatives were synthesized by the three component reaction of isatin derivatives,6-hydroxyaurone and?-Amino acid.The influence of temperature and solvent on the yield of the reaction was explored,and the optimal conditions were screened out.30 dispiro[benzofuran-2,2'-pyrrolizine-3',3''-oxindoles]derivatives?TM-26^TM-55?were synthesized under optimal conditions,with a yield of up to 83%.The structures of the products were determined by ¹H NMR,¹³C NMR and elemental analysis,The molecular structure was further confirmed by X-ray single crystal diffraction of TM-52,and the possible reaction mechanism was proposed.17 target products were selected to study the activity of its anti tobacco mosaic virus?TMV?.The activity test showed that the anti-TMV activity of TM-49 and TM-43 was similar to that of the control drug ningnanmycin.The method requires no catalyst,short reaction time and high yield,and the target compound has high anti-TMV activity.It is worth further study.