Reaction of protoberberine-type alkaloids. Part 12. A facile method for regiospecific oxygenation and excited oxidative ring-cleavage of berberine alkaloids

Abstract

Regiospecific photo-oxygenation and photo-oxidative ring-cleavage of protoberberine alkaloids is described. Irradiation of a solution of dihydroberberine (1) in the presence of Rose Bengal under aerated conditions gave 13-oxidoberberine (3) along with berberine (2) in 80 and 7% yields, respectively. In contrast, 7,8-dihydrocoralyne (5) gave 13-oxidocoralyne (7) in nearly quantitative yield when an aerated solution of (5) was heated in the dark. Irradiation of a solution of (3) containing Rose Bengal with visible light afforded 8,13a-epidioxy-9,10-dimethoxy-2,3-(methylenedioxy)-13-oxo-5,6,13,13a-tetrahydro-8H-dibenzo[a,g]quinolozine (11) in 90% yield. Under the same conditions, however, (7) gave 2′-acetylpapaveraldine (14) in 88% yield. On the other hand, when an alcoholic solution of (5) or (7) containing sodium alkoxide was irradiated with a mercury lamp (Vycol filter) under bubbling oxygen, 6,7-dimethoxyisoquinolone (15) and 3-alkoxy-5,6-dimethoxy-3-methylisobenzofuran-1(3H) one (17) or (18) were obtained in moderate yields. A reaction mechanism which involves the initial formation of an epidioxy-intermediate was evidenced by the fact that the photolysis of (7) was carried out in the presence of borohydride anion to give (15) and 5,6-dimethoxy-3-methylisobenzofuran-1(3H)-one (19). Irradiation of (11) in the same fashion gave berberal (20) and 2-(2-formyl-3,4-dimethoxybenzoyl)-3,4-dihydro-6,7-(methylenedioxy)isoquinolin-1(2H)-one (21) in 72% and 4% yields, respectively. Possible mechanisms are also presented.Reduction of (3) with sodium borohydride gave (±)-ophiocarpine (9) and (±)-13-epiophiocarpine (10), with the ratio (9) : (10) varying depending upon the nature of the alcohol used as solvent. An interpretation which rationalizes these observations is suggested.