Rhoeadine alkaloids indenobenzazepines

Analogous results were obtained from the reaction of another cycloberbine (183), as depicted in Scheme 33 (102-104). These reactions were applied to synthesis of indenobenzazepine (Section V,F,5) and rhoeadine alkaloids (Section V,G,2). 

Rearrangement of spirobenzylisoquinolines, having a hydroxyl group on ring C trans to the nitrogen, to indenobenzazepines was first reported by Irie et al. (209,210) in their synthesis of rhoeadine alkaloids (Section V,G,1). This... 

The first synthesis of a rhoeadine alkaloid was achieved by Irie et al. (209,210) through skeletal rearrangement of a spirobenzylisoquinoline to an indenobenzazepine. The trans-alcohols 434 and 329 were treated with methanesulfonyl chloride and rearranged to the indenobenzazepine 435,... 

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

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... 

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. 

A close relationship exists between the alkaloids of the two families Papaveraceae and Fumariaceae. Their relationship, as well as their independence, is particularly well demonstrated by the external structure of the flowers and various anatomical characteristics of different organs (Novak and Preininger 1983). Characteristically, the Fumariaceae contain spirobenzylisoquinoline (7), indenobenzazepine (8), se-cophthalideisoquinoline (10) and phthalideisoquinoline (9) alkaloids, whereas rhoeadine (11), pavine (12) and isopavine (13) type alkaloids, which are characteristic of Papaveraceae, are absent. The secoberbines have been found in C. incisa (Thunb.) Pers. and in C. ochotensis Turcz. (37—39). The cularine alkaloids (40) which are characteristic of the genus Corydalis are also found in species of Dicentra which is a member of the Papaveraceae. 

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