Protopine, isoquinoline alkaloids

Uterine relaxation effect Protopine Isoquinoline alkaloid 791... 

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. 

Depending on the reaction medium some cyclic alkaloids behave as ring enlarged or as ring contracted compounds. In Scheme VIII/19 indole alkaloids vomicine and perivine, the isoquinoline alkaloid protopine, and pyrrolizidines are given with their ring contracted forms. 

The Rutaceae are known as a large plant frunUy with approximately ISO genera and 1,000 to 2,000 swedes, chemically characterized by numerous alkaloids of extensive structural diversity. Some isoquinoline alkaloids are known in this family of which especially aporphines, protopines, protoberberines, and benzo[c]phenanthridines are common in the Papave-... 

Figure 7. Isoquinoline alkaloids, sanguinarine, chelerythrine and protopine isolated from Sangunaria canadensis with activity against H. pylori.

The leaves of this shrub gave berberine, (— )-tetrahydropalmatine, and protopine. The bark gave berberine, obaberine, and two new bisbenzyl-isoquinoline alkaloids 0-methylisothalicberine, C38H42O6N2 (mp 208° ... 

In Ottawa he began a systematic investigation of Fumariaceous plants for their alkaloid content. By developing new methods of separation of the alkaloids he found many new bases of the aporphine, benzophenanthridine, phthalideisoquinoline, protopine, and protoberberine ring systems. Three new classes of isoquinoline alkaloids also owe their discovery to this work. In his examination of Dicentra cucullaria he found the alkaloid cularine, determined its structure, and thereby demonstrated that it belonged to a new ring system. In the same period he isolated many of the alkaloids that are now known as the spirobenzylisoquinolines. Some 25 years later he was... 

Opitim contains 10-25% alkaloids, and the main constituent is morphine. Other than morphine, more than 25 alkaloids are known, and among them are other morphinan-type alkaloids (codeine and thebaine), benzyl-isoquinoline-type alkaloids (papaverine and noscapine), and protopine-type alkaloids (protopine). The biosynthetic precursor of all of these alkaloids is phenylalanine. 

Fig. 2 Densitogram and videoscan from 2D-TLC of isoquinoline alkaloids separated on silica layer by use of aqueous methanol (8%) with 1% ammonia as the first direction eluent and multicomponent non-aqueous eluent with 0.1 M DBA as the second direction eluent. N—noscapine, Na—narcotine, Nc—narceine, G—glaucine, E—emetine, C—codeine, P—papaverine, Pr— protopine, T— tubocurarine. Source From the effect of chromatographic conditions on the separation of selected alkaloids on silica layers, in J. Planar Chromatogr. ...

Fourteen isoquinoline alkaloid compounds (e.g., pavine, califomidine, carya-chine, aporphine, glaucine, protopine, allocryptopine, benzophenanthridine, cheli-rubine, sanguinarine) were extracted from Eschscholtzia californica and analyzed using a Cg column (A = 280 nm and positive ion MS/MS) using a complex 55-min 60/40 0/100 water (1 mM sodium dodecylsulfate with 10 mM triethyl amine to... 

Recently, Kulp et al. observed a similar behavior in CZE analysis of isoquinoline alkaloids in extracts of Chelidoniwn majus L. [14]. These compounds exhibit distinct anti-inflammatory, antimicrobial, and antitumor activities, and the most effective alkaloid components of the plant are protopine, chehdonine, coptisine, sanguinarine, allocryptopine, and chelerythrine. Being strongly basic molecules with a heterocychc-bound nitrogen, these compounds show pKa values above 5 thus, in acidic... 

Summarizing the data in this chapter one cannot conclude that generally benzyl-isoquinoline alkaloids are stored within the cells or excreted into the medium. It may be that specific types like the protopines or the benzophenanthridines are released into the medium whereas others like the protoberberines are deposited in the vacuole. 

The incorporation of dopa (60) has been further studied by examining its utilization in the formation of berberine (66) and hydrastine (67) in Hydrastis canadensis, corydaline (68) and protopine (70) in Corydalis solida, and ochotensimine (71) and protopine (70) in C. ochotensis.20 [2-14C]Dopa [as (60)] was again found to label only the isoquinoline moiety of these alkaloids (label is shown by ). 

The protopine alkaloids have a 10-membered ring containing a carbonyl group and a tertiary nitrogen atom. Even though they do not have an isoquinoline ring they are properly classified in the isoquinoline family... 

The synthesis of the parent ring-system of the protopine alkaloids using Perkin s method has been described.224 The preparation of examples of the indeno[l,2-c]isoquinoline ring system (219), exhibited by a rearrangement product of cryptopine, has been described.225 The transformation of protopine to benzophenanthridine alkaloids will be described in Section 3 J. 

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. 

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