Epoxy Indole Ring Opening To Build 3-sulfide Indole And 3-ester Base Indole Reaction Research

Indole is an important skeleton of many active molecules and it can binds to the target with high affinity.Among them,3-thioether indole is an important indole derivative,which is widely used in medicine,agriculture,materials and so on.Synthesis of C-S bond of indole position 3has also been reported extensively.In previous reports,the direct introduction of indole into CS bond at site 3 requires the use of noble metal reagents,toxic iodine and other corresponding catalytic systems to promote the reaction.From the economic,green point of view,It is the goal of scientists to find an efficient way to construct C-S bond and it is essential to develop synthetic methodologies that adapt to social development and have wide application.This method of epoxy indole ring opening after the indole pre-functional group,the reaction substrate has the advantages of good stability and mild reaction conditions so on.However,only aniline,phenol and 1,3-dicarbonyl compounds were studied by this method in previous reports.Therefore,this paper will carry out a more detailed study on the method of applying epoxy indole open ring to the indole functional group modification.Firstly,the method of C-S bond construction by epoxy indole opening ring under basic condition was studied,Through Several aspects of research about the optimization of reaction conditions,the range of substrate applicability of the reaction,gram scale amplification experiment and synthesis of active compounds containing 3-thioetheryl indole skeleton.Finally,the optimal reaction conditions under basic conditions were determined,thirty-two kinds of 3-thioether-indole skeleton compounds were synthesized and have medium to good yield(45%-97%).In addition,the synthesis of compounds with tubulin inhibitor activity was also studied,and prove the method has the potential to synthesis of active compounds.3-ester indole is also an important class of indole derivatives,and widely exist in some active molecules and functional molecules.In chapter 4,we studied whether the ring opening of epoxy indole could efficiently construct 3-ester indole.Finally,twelve kinds of 3-ester indoline skeleton compounds were synthesized successfully and have good yield(63-96%).This is the first report of the reaction of epoxide indoline ring under acidic conditions and greatly enriched the application of this methodology.This method does not need high temperature,can be carried out in the air atmosphere.It provides a green and efficient synthesis strategy for the construction of 3-thioetheryl indole and 3-ester indole,and a novel synthesis method for compounds containing such scaffolds.