Protoberberine alkaloids, transformation

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. 

Many methods have been developed so far for synthesis of protoberberine alkaloids (229). In this section interconversions of these alkaloids as well as transformations to nonnatural alkaloids are described. 

Although C—O bond cleavage is of little importance for transformations of protoberberines to other types of alkaloids, the selective C—O bond cleavage reaction provides access to naturally unabundant or nonnatural protoberberines from naturally abundant protoberberines such as berberine. 

Biosynthesis of the spirobenzylisoquinoline alkaloid ochotensimine (282) via the quinomethide intermediate (Scheme 49) was proposed by Shamma and Jones (7J0). On the basis of this hypothesis, several biomimetic transformations of phenolic protoberberines to spirobenzylisoquinolines have been realized by the base-induced rearrangement via the quinomethide. 

Phthalideisoquinoline alkaloids have been reviewed (1,2,176-179) and compiled (180). Because of the potential usefulness of phthalideisoquinoline alakloids such as bicuculline, a competitive antagonist of y-aminobutyric acid, many synthetic methods for these alkaloids have been developed. Several attractive transformations from protoberberines have also been reported. 

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

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