STEREOCHEMICAL STUDIES ON THE BIOSYNTHESIS OF PROTOBERBERINE, PROTOPINE, AND BENZOPHENANTHRIDINE ALKALOIDS USING PAPAVERACEAE PLANT-CELL CULTURES

In the cultured cells of Corydalis incisa, (-)-enantiomers of the alpha-N-metho salts of the trans- and cis- 13-methylprotoberberines having trans and cis configurations of the protons at C-13 and C-14, respectively, were stereospecifically bioconverted into the (-)- and (+)-13-methylprotopines [(-)-(13S)- and (+)-(13R)-enantiomers], respectively. The alpha-N-metho salts of the eight different 13-methylprotoberberines were demonstrated to be the precursors of the 13-methylprotopines, though there is a difference in conversion yields. The alpha N-metho salts of the trans-13-methylprotoberberines bearing a methylenedioxy bridge at C-2 and C-3 are more favorable precursors of the 13-methylprotopines than those having methoxyl groups at the same positions. The alpha-N-metho sales of cis-13-methylprocoberberines with either methylenedioxy or methoxy substitution are efficiently converted into 13-methylprotopines. The (+)-(13R)-13-methylprotopines were more effective precursors of the benzophenanthridines than the (-)-(13S)-methylprotopines. The 13-methylprotopines possessing a methylenedioxy bridge were more preferred precursors of the benzophenanthridines than those having methoxyl groups. (+)-Corynoline [14] is more easily oxidized than(-)-14, resulting in (+)-corynoloxine [18]. (-)-Corynoline is acetylated more easily than its (+) isomer to afford (-)-acetylcorynoline [19]. Corynoline analogue 15, having methoxy groups at C-7 and C-8, must not be as easily oxidized as corynoline, which has a methylenedioxy bridge at C-7 and C-8. (+)-Chelidonine [27] was converted into dihydrosanguinarine [32] and dehydrochelidonine [28]. Biotransformation of the protoberberines into the benzophenanthridines occurred similarly in both cultured cells and live whole plants of Co. incisa.