Rhoeadine and Papaverrubine Alkaloids

Synthetic work on rhoeadan and other benzazepine alkaloids has been reviewed. The synthesis of benzindenoazepines from l-benzoyl-3,4-dihydroisoquinolines cf. Vol. 6, p. 158) has been applied to the preparation of methylenedioxy analogues, e.g. (162). An alternative to the published procedure 

Kametani, M. Premila, S. Hirata, H. Seto, H. Nemoto, and K. Fukumoto, Canad. J. Chem., 1975,53, 3824. 

Reagents i, NaOMe-MeOH ii, aq. NaOH-DMSO iii, p-TsOH. 

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This material is supplementary to The Alkaloids, Vol. X, p. 474. Rhoeadine and papaverrubine alkaloids have been reviewed by Pfeifer et al. (397a). 

Formerly, rhoeadine and papaverrubine alkaloids were known to occur only in the plants of the genus Papaver. Recently, Slavik et al. have shown that rhoeadine and papaverrubine E are present in Bocconia frutescens and papaverrubine D in Meconopsis betonicifolia, M. horridula, M. napaulensis, M. paniculata, M. robusta, M. rudis, and M. sinuata (33, 50). The genus Meconopsis is botanically closely related to the genus Papaver, a relation thus confirmed chemotaxonomically (see structures 152-154 in Table V). 

The absolute configurations of all the rhoeadine and papaverrubine alkaloids have now been elucidated using the aromatic chirality method. For instance, ( + )-glaudine is represented by structure (191), (+ )-epiglaudine by (192), and ( + )-oreodine by (193). ... 

Alpinigenine has been isolated from the dried latex of Papaver bracteatum Rhoeadine, as well as other isoquinoline alkaloids, has been found in the aerial parts of P. fugax of Turkish origin. P. urbanianum has been shown to produce papaverrubine A thin-layer chromatographic procedure on talc has been developed for the separation of papaverrubines A, D, and E from P. rhoeas. Details concerning attempts to correlate results of c.d. studies of rhoeadine and related alkaloids (cf. Vol. 4) with those obtained by the aromatic chirality and... 

Rhoeadine and papaverrubine (norrhoeadine) alkaloids which were previously believed to occur only within the genus Papaver have now been found to be present in two other Papaveraceae genera, namely Bocconia and Meconopsis. In Bocconia frutescens L. rhoeadine alkaloids accompany a variety of protopine, protoberberine, and benzophenanthridine bases. ... 

A papaverrubine (possibly E) also found in trace amounts Known constituents, e.g. rhoeadine, and five unknown and unidentified alkaloids were also present Several papaverrubines were also present. 

Scheme 18. Mutual transformation of the erythro and threo series of rhoeadine-papaverrubine alkaloids by H+ catalysis and methylation (226, 4S3).

The genus Papaver differs substantially from other members of the Papaveraceae by the presence of rhoeadine-papaverrubine alkaloids and the genera Oorydalis, Dicentra and probably P )wana which, in addition to the common benzylisoquinoline alkaloids contained in this family, are also able to synthesize some alkaloids having an additional CH3 group (13-methyltetrahydroprotoberberine audits natural derivatives— see p. 384, and 13-methylprotopine—see p. 391). 

Alkaloids MR-2 and MR-3, allocryptopine, amurensinine. methohydroxide. base mp 212°, coptisine, corysamine, cryptopine, magnoflorine. norharmane alkaloid , papaverrubine D and E, protopine, rhoeadine, several unidentified alkaloids... 

A survey of the plants of this section and their alkaloids is given in Table V (31-37). The major alkaloids are rhoeadine (389) and protopine (309), the minor alkaloids are isorhoeadine (389) and the papaverrubines (396-400, 406). However, plants have also been found whose major alkaloids are aporphines. The presence of these alkaloids can be considered as a significant characteristic of the section Orthorhoeades. 

Of the six species classified by Fedde (70) in this section, only P. mac-rostomum Boiss. et Huet. has been studied (Table VII). The other species are morphologically closely related (46). Plants cultivated in central Europe (CSSR, GDR), were found to contain rhoeadine, papaverrubine, and protopine alkaloids in the same way as the species of the sections Orthorhoeades and Argemonorhoeades (40,47). Plants collected in the vicinity of Lake Sevan (Armenia) yielded macrostomine (40) as the major alkaloid together with dehydronor-macrostomine (43) and sevanine (37) (benzylisoquinolines of the papaverine type) but no rhoeadines or papaverrubines (48). These differences in the alkaloid content may be explained by the observation that P. macrostomum from Armenia... 

Studies of plants from the section Argemonorhoeades show that these plants contain only a very few alkaloids including those of the protoberberine (5), rhoeadine (11), papaverrubine and protopine (3) types. These alkaloids are similar to those found in the section Orthorhoeades but they occur in markedly lower yields. 

The genus Bocconia of the tribe Chelidonieae comprises some 10 species which are native to tropical and subtropical areas of Central and South America. Bocconia, which is closely related to the East Asian germs Macleaya, does not appear to contain alkaloids which are taxonomicaUy significant although it may be noted that rhoeadine (18) and papaverrubine E have been isolated from B. frutescens L. (Slavik and Slavikova 1975). 

Coptisine, isorhoeadine, oxysanguinarine, papaverrubine D, E, protopine, rhoeadine, rhoeagenine. Alkaloid PA-1, and base (mp 283° dec)... 

Alkaloid MR-1, MR-3, allocryptopine, coptisine, corysamine, magnoflorine, papaverrubine D and E. protopine, rhoeadine Alkaloids MR-1 and MR-3, allocryptopine, coptisine, corysamine, magnoflorine, papaverrubine D, protopine Alkaloids MR-1 (C Hi O), MR-2, MR-3, and MR-4, allocryptopine. amurensinine methohydroxide, coptisine, magnoflorine, papaverrubine D and E, protopine, rhoeadine ( )... 

Alkaloid PO-5, alborine, amurensine, amurensinine, cryptopine, mecambridine, mecambridine methohydroxide, papaverrubine C, D, and E, protopine, rhoeadine... 

The following groups of alkaloids occur in the plant family of the Papaveraceae benzylisoquinoline, cularine, aporphine, proaporphine, morphine, protoberberine, protopine, narceine, benzophenanthridine, phthalide-isoquinoline, rhoeadine, papaverrubine, pavine, isopavine and ochotensimine. Many of these alkaloid groups are formed by one genus only, whereas others occur in many genera and even in plants of other families. Alkaloids of all these groups must thus be taken into considera-... 

Pfeifeb, S., I. Mann, and L. Kuhn Alkaloide der Rhoeadin-Papaverrubin-Klasse. Basen mit einer neuen Grundstruktur. Pharm. Zentralhalle 107, 1— 27 (1968). 

There are a series of rhoeadine-type alkaloids including rhoeadine itself (8) and the nor-alkaloids known as the papaverrubines (Pfeiffer 1966, Dolejs and Hanus 1967). These alkaloids are of no medical importance. 

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