Secoberbine Alkaloids

All the 7,8-secoberbines incorporate an JV-methyltetrahydroisoquinoline moiety with two or three oxygenated substituents at C-l, C-2, and C-3. The lower aromatic ring possesses four substituents in a vicinal arrangement of which two are alkoxyls and the third the berbine bridge carbon. The latter may occur in different oxidation states as an aldehyde (in 1 and 2), an alcohol (3-6, 8, 9), or a carboxylic acid (7). 

The immonium system 11 has been examined by Czech authors (22,24,25), who claimed that it reacts with hydroxide ions in aqueous media to form pseudobases. This implies that hypecorine (8) and hypecorinine (9) may be artifacts of isolation. In all probability, the quaternary immonium system 

The structures of these bases have been established mainly on the grounds of their physicochemical data and have been confirmed by synthesis. In Table II the melting points, specific rotations, absolute configurations, and IR and UV spectral features are collected. 

Some Physical and Spectral Data of 7,8-Secoberbine Alkaloids 

In many syntheses of 7,8-secoberbines other isoquinoline alkaloids have been used as substrates. 

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Regioselective C-8—N bond cleavage of protoberberines is a crucial step for synthesis of secoberbine alkaloids (2). 

The 6,7-secoberbine alkaloids contain the four following natural products corydalic acid methyl ester (55), corydamine (56), N-formylcorydamine (57), and hypecumine (58). These bases, called 3-arylisoquinolines, were described by Shamma and Moniot (2) as a separate class of isoquinoline alkaloids. Santavy (7) classified them among benzophenanthridines. It seems, however, that they may be considered as biosynthetic intermediates between the protoberberines on the one hand and the benzophenanthridines on the other. 

Some Physical Data and Spectral Characteristics of 6,7-Secoberbine Alkaloids... 

Several transformations of 6,7-secoberbine alkaloids to their parent congeners were conducted. Corydalic acid methyl ester (55) was converted to (+)-mesotetrahydrocorysamine (72) (65) (Scheme 18), and corydamine (56) was transformed to tetrahydrocoptisine (39) 64) (Scheme 19). 

C-9, and C-10, always with a phenolic hydroxy group at the 8a position. Moreover, they differ from one another by the oxidation state of the benzylic C-13 as well as by substitution and degree of saturation of the isoquinoline fragment. These alkaloids, classified as benzylisoquinoline alkaloids (2,70-74), have recently been called by Shamma et al. (75-77) pseudobenzyliso-quinolines originating from protoberberine alkaloids. In Table V a list of 8,8a-secoberbine alkaloids, sources, and spectral data are presented. 

Plants of the subfamily Hypecoideae differ chemotaxonomically from the plants of the subfamily Papaveroideae. Species of the genus Hypecoum contain secoberbine alkaloids (37-39) in addition to protopine (3), protoberberine (5) and benzophenanthridine (6) alkaloids. The presence of secoberbines (37-39) is indicative of a close relationship between Hypecoum and some species of Fumariaceae. 

The protoberberine alkaloids (5-75) play important roles as precursors in the biosynthesis of a variety of related isoquinoline alkaloids such as protopine, phthalideisoquinoline, spirobenzylisoquinoline, rhoeadine, inde-nobenzazepine, secoberbine, and benzo[c]phenanthridine alkaloids. Chemical transformations of protoberberines to these alkaloids are particularly interesting and exciting from the biogenetic viewpoint and further from ready availability of starting protoberberines in nature or synthesis. 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

Three syntheses of 6,7-secoberbines have been carried out. Two of them involved degradation of the protoberberine alkaloids (63,65), and the third was a total synthesis (69). Takao and Iwasa (63) applied the von Braun reaction to tetrahydrocoptisine (39) to obtain the 6,7-seco bromide 63, which on treatment with dimethylamine, followed by hydrolysis, gave tetrahydro-corydamine (64). This tetrahydrobase 64, which was also produced from 56 by zinc in hydrochloric acid (63), was dehydrogenated to corydamine (56) (Scheme 15). 

S)-(+)-reticuline (20) and orientaline (25). The alkaloids of the Papaveraceae and Fumariaceae can be subdivided into several constitutional types (Fig. 3), viz., simple isoquinolines, benzylisoquinolines, pavines, isopavines, cularines, proaporphines, aporphines, promorphinanes, morphinanes, protoberberines, retroprotoberberines, secoberbines, benzophenanthridines, protopines, phthali-deisoquinolines, secophthalideisoquinolines, indenobenzazepines, spirobenzyl-isoquinolines, and rhoeadines. 

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