Biosynthesis of Berberine and Berberastine Incorporation of Catecholamines

Abstract

A B S T R A C T Dopamine serves as a precursor o f berberastine, berberine, hydrastine, and canadine i n Hydrastis canadensis L. Noradrenaline serves as a precursor o f berberastine b u t is not incorporated into t h e other three bases. I t is shown t h a t t h e incorporation o f labelled doparnine into berberine and o f labelled noradrenaline into berberastine takes place without randomization o f radioactivity.Two C6-C2 units, derived froin tyrosine, are incorporated into the alkaloids which are biogenetically related to norlaudanosoline. The carbon slceleton of some of these bases (e.g., papaverine (3) and morphine (4)) is accounted for in its entirety by two such units.T o coinplete the slceleton of other bases belonging to this group (e.g., hydrastine (5, 6), narcotine (7), berberine (6, 8), and chelidonine (9)) an additional one-carbon unit is required, which is derived from the S-methyl group of methionine (10).We have presented evidence that the two C6-C2 units differ from one another. T h e first experimental indications came from our finding that even though tyrosine gave rise t o both of the C6-C2 units which are incorporated into hydrastine the efficiency of incorporation of the two units was unequal (5), and from the results of Rapoport, Levy, and Stermitz on the nonrandom incorporation of carbon dioxide into morphine (11). We obtained direct evidence for the inequality of the two C6-Cz units in the biosynthesis of hydrastine with the demonstration that 3,4-dihydroxyphenylethylamine (dopanline) supplied only one of these units (12). Analogous results have now been reported by Leete and i\ilurrill and by Battersby and Francis in studies of the biosynthesis of chelidonine (13) and of morphine (13,14). I t appears that the conversion of tyrosine into dopa (15) and thence into two dissimilar intermediates, presumably dopainine and 3,4-dihydroxyphenylpyruvic acid, represents a common early stage of the routes leading t o the different structural variants among the alkaloids related to norlaudanosoline (XII). In extension of the evidence for the generality of this biosynthetic pathway we now report that dopamine supplies only one of the two C6-C2 units which are incorporated into berberine.Six small plants of Hydrastis canadensis L. were allowed t o grow for 6 days with their roots immersed in aerated nutrient solution containing l-14C-dopamine hydrobromide (expt. 1). Berberine and hydrastine were extracted from roots and rhizomes by standard methods (6), and were found to be radioactive. Radiochemical yields in this experiment were of the same magnitude as those obtained in a n earlier experiment with the same precursor (ref. 6, expt. lo), even though the duration of the feeding, the modes of administration of tracer, and the number and size of the plants and therefore also the chemical yield of alkaloids were different. In Table I

Goldenseal (Hydrastis canadensisL.) Extracts Synergistically Enhance the Antibacterial Activity of Berberine via Efflux Pump Inhibition

“…1 is that reported for the standard, but the configuration of the canadine standard was not confirmed. The isolation of a ± mixture of canadine from H. canadensis has been previously reported [26], but it was not possible with the LC-MS method employed to distinguish stereoisomers of hydrastine or canadine. Alkaloids were found in higher concentrations in root than in leaf extracts (l " Table 1).…”