8.8- Secoberbine alkaloids synthesis

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

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). 

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