Protopine from Chelidonium majus

Additional oxidative coupling processes among the various methylated derivatives of laudanosoline yield many other families of bases, including the pavine argemonine (88) from Argemone mexicana E berberine (89) from Hydrastis canadensis E which, despite its toxicity, has been used as an antimalarial protopine (90) and chelidonine (91) from Chelidonium majus E rhoeadine (92) and the cephalotaxus ester harringtonine (93) from Japanese plum yews ( Cephalotaxus spp.), which is a compound of some significance because it possesses potent antileukemic activity (see Fig. 3). 

The benzophenanthridine skeleton is encountered in approximately 30 alkaloids, principally of the family Papaveraceae (Cordell, 1978a). In contrast to the biosynthesis of protopine alkaloids, phenanthridine alkaloids are synthesized in the cytoplasm (Hartmann, 1991). This type of system arises from a protoberberine precursor by fission of the C-6-N bond and recyclization. The biogenetic sequence leading to chelidonine (80) biosynthesis in Chelidonium majus has been supported by feeding experiments with multiply-labeled (-t-)-reticuline [(5)-reticuline] (20) and with labeled stylopine (79) (Fig. 32.25) (Hutchinson, 1986 Sim ek, 1985 Tanahashi and Zenk, 1988). (5)-Z-V-Methylstylopine and protopine (60) have been shown to be metabolites in this pathway. Reticuline is oxidatively cyclized to ( —)-scoulerine (72). Formation of two methylenedioxy groups results in the formation of stylopine (79) (Hartmann, 1991). 

Fig. 36.3 Chemical structures of sanguinarine and coptisine and CZE separation of seven alkaloids in an extract of Chelidonium majus L. Peaks (7) sanguinarine, (2) coptisine, (3) chelerythrine, (4) stylopine, (5) chelidtmme, (6) protopine, (7) allocryptopine, and (x) unknown component. Conditions 20 mM phosphate buffer, pH 3.1. Separation capillary 75 pm, i.d. uncoated fused silica, 50 cm in length (40 cm effective length). Applied voltage 16 kV. Light-emitting-diode-induced fluorescence (LED) excitation wavelength 280 nm (Modified from reference [14])...

Reticuline is a precursor of sinomenine, via sinocutine, in Sino-menium acutum (115). It is also a precursor of berberine (LXI) in Hydrastis canadensis L. and of protopine (LXII) in Dicentra spectabilis (L.) Lem. (116). In the case of the former base the i T-methyl group of reticuline is used to form the berberine carbon (carbon atom 8) of the tetracyclic alkaloid and with the latter base it is found as the same carbon atom in the heterocyclic ring of protopine. By feeding multiple-labeled (+ )-reticuline, as indicated in LXIII, to Chelidonium majus L., it was shown that it is a precursor of chelidonine (LXIV), (— )-stylopine (LXV), and protopine (LXII), and that the labeled atoms are found in the places expected from current biogenetic theories (117). 

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