The Protoberberines and Retroprotoberberines

Most protoberberine alkaloids occur in nature as tetrahydroprotober-berines or as quaternary protoberberinium salts. However, in the last few years a number of quaternary iV-methyltetrahydroprotoberberine salts as well as 7V-oxides have been reported. In addition to the usual substitution pattern, the C-8 position may bear a methyl group as in the naturally occurring protoberberine alkaloid ( —)-corytenchirine. Two recently reported retroprotoberberines are TV-methyl- and iV,(9-dimethylmecambridine the chemistry, synthesis, pharmacology, and biogenesis of the protoberberine alkaloids have been reviewed. 

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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. 

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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