Studies On Synthesis Of Tetracyclic Quaternary Ammonium Salts And Ketoamide Derivatives From Isoquinoline Derivatives

Isoquinoline and its derivatives are important heterocyclic compounds,which are found in many natural products.In 1848,papaverine was firstly extracted from Papaveraceae.Papaverine was an isoquinoline alkaloid with antimicrobial activity and antiviral activity,it was used as an antispasmodic until now.Berberine was extracted from rhizome of Coptis Chinensis or other plants,and it was mainly used as antibacterial,anti-cancer and antiarrhythmic agent in clinical.In recent years,isoquinoline skeletons are often used to design active structural groups in drug molecules,such as atracurium,mosavirin,isoquinaine,etc.Studies of synthesis,partial structural modification and structure-activity relationships of isoquinolines and their derivatives have become more active.In this paper,we focus on isoquinoline,and introduce the strategy of efficiently synthesizing tetracyclic quaternary ammonium salts and ketoamides from isoquinoline derivatives.The specific work is as follows:1.Rh-catalyzed synthesis of tetracyclic isoquinolinium salts via C-H activation and [4+2] annulation of dihydroisoquinolines and alkynes.Tetracyclic quaternary ammonium compounds exhibit significant antibacterial and anticancer activities.Therefore,it is very important to develop the synthesis methods of such compounds.Cyclic imines was used as directing group to synthesize tetracyclic isoquinolinium salts via C-H activation and [4+2] annulation of dihydroisoquinolines and alkynes catalyzed by Rh.The method is simple,rapid and efficient,the yield of obtained products is very high,some yield could achieve 99% in 10 min.In gram-scale reaction of 2.1a with 2.2a,4.505 g of 2.3aa was obtained in 99% yield in 22 h when the S/C = 10,000.This provides an effective strategy for the synthesis of tetracyclic isoquinoline salts.2.Synthesis of ketoamides via hydrolysis of dihydroisoquinoline compounds and acid chloride compounds.In this part,different ketosulfonamides and ketoamides are efficiently synthesized by the reaction of dihydroisoquinoline compounds with(sulfonyl)chloride compounds,and the reaction also avoided self-oxidation of dihydroisoquinoline compounds.This method is green and has good substrate compatibility without any use of metal catalyst.This method provides an efficient strategy for the synthesis of ketoamides.