Total Synthesis Of Oxoaporphine Alkaloids Liriodenine,Dicentrinone And Cassameridine

The alkaloids are widely distributed in nature,and are favored by chemists for their various physiological activities.Liriodenine,Dicentrinone and Cassameridine are typical oxoaporphine alkaloids,which have extensive physiological activities.In this paper,new total syntheses of oxoaporphine alkaloids such as liriodenine,dicentrinone and cassameridine were developed.The key step of these total syntheses is copper-catalyzed conversion of 1-benzyl-3,4-dihydro-isoquinolines to 1-benzoyl-isoquinolines,This copper-catalyzed conversion is mild,easy to operate,high yield and environmental protection.The new total synthesis of alkaloids Liriodenine,Dicentrinone and Cassameridine are described as follows:(1)First of all,pepper ethylamine was obtained by two steps from the cheap piperal.Then,pepper ethylamine and o-nitrophenylacetic acid were transformed into the amide ?-6a.Dihydroisoquinoline was produced by Bischler-Napieralski reaction,which was used for benzylic oxidation and aromatization without separation to give ?-8a.Subsequently,?-8a was reduced to amine by iron powder and the Pschorr cyclization reaction was finally used to synthesize Liriodenine(?-la)with an overall yield of 39%(7 steps).(2)Pepper ethylamine and 2-nitro-4,5-dimethoxy phenylacetic acid were transformed into the amide ?-6b.Dihydroisoquinoline was produced by Bischler-Napieralski reaction,which was used for benzylic oxidation and aromatization without separation to give ?-8b.Subsequently,?-8b was reduced to amine by iron powder and the Pschorr cyclization reaction was finally used to synthesize Dicentrinone(?-1b)with an overall yield of 26%(7 steps).(3)Pepper ethylamine and o-nitropiperacetic acid were transformed into the amide ?-6c.Dihydroisoquinoline was produced by Bischler-Napieralski reaction,which was used for benzylic oxidation and aromatization without separation to give ?-8c.Subsequently,?-8c was reduced to amine by iron powder and the Pschorr cyclization reaction was finally used to synthesize Cassameridine(?-1c)with an overall yield of 29%(7 steps).