Study On Decarboxylation Of Indole-3-acetic Acids And Biological Activity Of Products

Indole is a kind of N-heterocycle which is widely present in nature.It displays extensive biological activities with its own physicochemical properties and biological characteristics,which plays an important role in medicine.In this thesis,we review the applications of indole-containing active small molecules in the field of medicine,and find that indolmethyl-containing molecules take important position in them.After summarizing,we found the current methods for synthesizing indolmethyl compounds were limited.To realize functional group by decarboxylation is an important means in organic synthesis,which has a history of more than two hundred years.Especially in recent years,the transition-metal catalyzed decarboxylation reaction has been greatly developed.Based on the previous works,herein,we designe indole-3-acetic acids as the source to introduce indolmethyl into different substrates,and sythesize more indolmethyl compounds with potential pharmacological activity.In chapter 2,we developed a copper-mediated the decarboxylation coupling of indole-3-acetic acids with pyrazolinones.After optimizing reaction conditions,we found that indole-3-acetic acids and pyrazolinones can obtain a good yield with 2 equivalent Cu(OAc)2·H2O as oxidant,DMF as solvent,under 90 ℃ in the atmosphere of N2.This reaction is the first example about direct C4 indolmethylation of pyrazolones.Under optimal reaction conditions,we investigated the functional group tolerance of pyrazolinones and indole-3-acetic acids,the results showed that the reaction had good functional group tolerance.We obtained 33 decarboxylation coupling products.The preliminary biological activity experiment showed some compounds possessed inhibitory activity on tumor cells and products 2-3af and 2-3ag also had inhibitory activity of influenza virus.In chapter 3,we investigated a copper-mediated the decarboxylation of indole-3-acetic acids and o-hydroxyaryl enaminones,and successfully synthesized 3-indolemethyl-chromones.o-Hydroxyaryl enaminones were used as the precursor substrate of chromones,which cyclized with indole-3-acetic acids to form 3-indolemethyl-chromones.In order to improve the efficiency of the reaction,we successfully designed the synthetic methods of 3-indolemethyl-chromones from o-hydroxy acetophenones with a two-step,one-pot method.In addition,we further derivatized some 3-indolemethyl-chromones to obtain pyrimidinine-containing indolemethyl compounds.And we also evaluated the inhibitory activities of the products on tumor cells and influenza virus by cell inhibition experiments.In chapter 4,we investigates a copper-mediated oxidative decarboxylation coupling of indole-3-acetic acids with a-C-H of aldehydes and ketones.The reaction successfully achieved the α-benzylation of aldehydes and ketones at 90℃ by using a copper/amine synergistic catalysis.The substrate applicability of the reaction was good,whether cyclic aldehydes and ketones,branched aldehydes and ketones,or aromatic ketones were compatible in the reaction.Besides 3-indoleacetic acids,other types of arylacetic acid,such as o-nitrophenylacetic acid can also be smoothly converted in the reaction.And by changing the reaction conditions,we can selectively obtain dibenzylated products.In addition,we derivatized some products into tetrahydrocyclopentyl[b]indole derivatives,the structures of which are widely found in natural products,and we also studied the inhibitory activity of the products on tumor cells.