Palmatine, conversion

Oxidative conversion of palmatine, berberine, and coptisine to polycarpine, polyberbine, and its analog was described in Section II,B. These products were further transformed to aporphine alkaloids having a phenolic hydroxyl group at C-2 in the bottom ring (55). Hydrolysis with concomitant air oxidation of polyberbine (66) furnished 3,4-dihydrorugosinone, which was further air-oxidized in ethanolic sodium hydroxide to give rise to rugosinone (501) (Scheme 105). Successive reduction of the enamide 68 with lithium aluminum hydride and sodium borohydride afforded a mixture of ( )-norledecorine and (+ )-ledecorine (502). N-Methylation of the former with formaldehyde and sodium borohydride led to the latter. 

It is known that berberine (46) and the protoberberine alkaloid (S)-stylopine (44) are elaborated from an intact molecule of (S)-reticuline [as (33)], the 7V-methyl group providing C-8 in each alkaloid1,2,42 (cf. Vol. 7, p. 12). Exactly similar findings were obtained for tetrahydropalmatine (45) and palmatine (47) in C. laurifolius.43 Of several benzylisoquinolines tested, only reticuline (33), nor-reticuline (41), and norlaudanosoline (40) were significantly incorporated. Tetrahydropalmatine (45) was found to be converted into palmatine (47) and the conversion was irreversible. 

Introduction of an alkyl group at the C-13 position of the protoberber-ine ring system is readily accomplished by direct alkylation of either the 8-acetonyl base 77) or the dihydro derivative (78) of the appropriate alkaloid. Reduction of the resulting salt, usually without isolation, affords the corresponding epimeric 13-methyltetrahydro bases. The conversion (79) of palmatine (V) to corydaline (VI) and mesocorydaline (VII) via the salt VIII exemplifies the use of this reaction which constitutes an early example of the now well-known C-alkylation of an enamine. 

The conversion of tetrahydroberberine into tetrahydropalmatine, first achieved by Spath and Lang, is described elsewhere (p. 292). By demethylenating berberine sulphate Sp th and Quietensky obtained the dihydric phenolic base (XXV R = R = H), which on complete 0-methylation yielded palmatine (XXV R = R = Me), and on partial methylation gave jatrorrhizine (XXV R = H R = Me), the latter being isolated and identified as di-tetrahydrojatrorrhizine (p. 291). Columbamine is represented by (XXV R = Me R = H). A complete synthesis of palmatine was effected by Haworth, Koepfli and Perkin, who condensed 3 4-dimethoxyAomophthalic anhydride with 8-veratryl-ethylamine to -j8-veratrylethyl-3 4-dimethoxy omophthalamic acid, the methyl ester (XXVI) of which was converted by treatment with phosphorus oxychloride into oxypalinatine (XXVII), CjiHjiO N, buff-coloured prisms, m.p. 183°. This behaves like oxyberberine (XXII, p. 335), and on electrolytic reduction yields dZ-tetrahydropalmatine, m.p. 147°, which on oxidation with iodine in alcohol furnished palmatine (XXV R = R = Me) in the form of the iodide, m.p. 241° (dec.). 

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