Protoberberines aporphines alkaloid

Misik, V., L. Bezakova, L. Malekova, and D. Kostalova. 1995. Lipoxygenase inhibition and antioxidant properties of protoberberine and aporphine alkaloids isolated from Mahonia aquifolium. Planta Med. 61 372-373. 

In a pair of back-to-back papers, the author and co-workers first reported the isolation and characterization of thalibealine (70), a novel tetrahydro-protoberberine-aporphine dimeric alkaloid from Thalictrum wangii,143 That report was followed by a paper reporting the synthesis of thalprezwalskinone (71) and a revision of the structure of that alkaloid.144... 

Nicotine and related pyridine alkaloids (A) Ammodendrine (A) anabasine (A) arborine (AA) boldine and other aporphine alkaloids (AA) berberine and related protoberberine alkaloids C-toxiferine (AA) coniine and related piperidine alkaloids (A) cytisine, lupanine, and other quinolizidine alkaloids (A) tubocurarine (AA) codeine (A) erysodine and related Erythrina alkaloids (AA) histrionicotoxin (AA) lobeline (A) methyllycaconitine (AA) pseudopelletierine (A)... 

Because benzylisoquinolines have been available synthetically (in racemic form) for decades, there is quite a bit of chemistry known regarding their use as key intermediates in the synthesis of a number of more complex isoquinoline alkaloids. The asymmetric synthesis of benzylisoquinolines has been used to complete total synthesis of representative members of several of these alkaloid classes. As shown in Figure 6, the protoberberine alkaloid norcoralydine, the aporphine alkaloid ocoteine, the isopavine alkaloid reframoline and the morphinan 0-methylflavinantine have been made available in optically active form for the first time (except by isolation or resolution) using this approach. 

Four protoberberine alkaloids and one aporphine alkaloid were evaluated for lipoxygenase inhibition. Oxyberberine and columbamine were the most potent lipoxygenase inhibitors tested, with jatrorrhizine being intermediate, whereas berberine and magnoflorine exhibited only low potencies. A strong linear correlation between lipoxygenase inhibition and lipid antioxidant properties of these alkaloids was observed. These data suggest that the mechanism of... 

A classification of the known alkaloids based on the individual tribes, genera, and sections (Table I) shows that all the investigated genera contain protoberberine, protopine, and benzophenanthridine alkaloids of the sanguinarine and chelerythrine type 195). There was also observed a frequent occurrence of the aporphine alkaloids. In the plant family Papaveraceae, the aporphine alkaloids having oxygen substituents in position C-8 are absent. None of these groups of alkaloids can be used for chemotaxonomic purposes. The enzymes which synthesize them are therefore ubiquitous for the whole family Papaveraceae. 

Cytotoxicity. In our published studies, several alkaloids were screened including benzyl isoquinolines, protoberberines, aporphines, and amides. Palmatine [56], norannuradhapurine (A-37) [56], kuafumine (A-64) [43], liriodenine (A-59) [56], atherosperminine (A-89) [56], argentinine (A-92) [40], annoretine (A-93) [40], A -lran -feruloytyramine (A-lll) [44,57], A-tranj-caffeoyltyramine (A-112) [57], N-p-coumaroyltyramine (A-113)... 

CycUzations. Bromoarenes form radicals that can be exploited in synthesis, including cyclization routes to aporphines-indolo[2,l-a]isoquinolines, and protoberberine-pavine alkaloids. ... 

The conversion of reticuline (41) into protoberberine alkaloids (coreximine and scoulerine), a morphinandienone alkaloid (pallidine), and an aporphine alkaloid (isoboldine) by rat-liver enzyme has been reported. ... 

The known chemistry of the Annonaceae is mainly based on the work of Cave and Leboeuf on the benzyhsoquinoline alkaloids. After this work, several papers were published which evidenced the presence of alkaloids derivatives of isoquinolines. Approximately 800 alkaloids of the types isoquinolines, protoberberine, aporphine, and others were isolated from different genera of the Aimonaceae. Previous chemical and pharmacological investigations have indicated that bisbenzylisoquinolines are important bioactive components existing in plants of the Annonaceae family. Other terpenes, flavonoids, Hgnans, acetogenins, and some aromatic compounds are also found in the family but the alkaloids are the major chemical constituents. 

Species of Glaucium are characterised by the presence of aporphine alkaloids in addition to the commonly occurring protopine (3), protoberberine (5) and benzophen-anthridine (6) alkaloids. In these respects, Glaucium resembles Papaver, Eschscholzia, Meconopsis mdRoemeria but it differs from the other genera of the Papaveraceae. 

Meconopsis comprises some 40 species which are mainly indigenous to China and the Himalayas. Protopine (3), protoberberine (5), benzophenanthridine (6), isopavine (13) and aporphine alkaloids (Fig. 2) have been isolated from a small number of species. Rhoeadine alkaloids, which are present in Papaver species, also occur in Meconopsis and their distribution appears to be limited to these two genera (Slavik and Slavikova 1977). The sole European representative, M. cambrica growing in England produces magnoflorine (4) as the major alkaloid, together with protoberberine (5), proaporphine (14) and promorphinan alkaloids (15) (Hemingway et al. 1981). 

Fibraurea and Tinomiscium both native to Asia contain the same types of protoberberine and aporphine alkaloids. 

As pointed out earlier, the structural diversity of this class of tyrosine-derived secondary metabolites arises from different aryl coupling reactions. The biosynthetic pathway to alkaloids of the protoberberine skeleton, as well as the aporphine and morphine skeleton, is outlined in Scheme 12.4 [14]. While protoberberine [18] and aporphine alkaloids [19-21] are obtained from (S)-reticuline (19), opium alkaloids are biosynthesized from the enantiomeric (/ )-configured natural product (20). 

Protoberberine alkaloids j Aporphine alkaloids j [ Opium alkaloids ]... 

Nicotine boldine and other aporphine alkaloids C-toxiferine coniine and other piperidine alkaloids cytisine and other quinohzidine alkaloids epibatidine tubocurarine Berbamine, berberine, and other isoquinoline alkaloids cinchonidine and other quinoline alkaloids corynanthine, yohimbine, and other indole alkaloids emetine ephedrine ergometiine and related ergot alkaloids Ergocornine and related ergot alkaloids bulbocapnine and related aporphine alkaloids anisocycline, stylopine, and related protoberberine alkaloids salsolinol and related isoquinohnes BicuculUne, cryptopine, hydrastine, and related isoquinoline alkaloids securinine harmaline and related beta-carboline alkaloids Corymine, strychnine, and related indole alkaloids Histrionicotoxin and related piperidines ibogaine and related indole alkaloids nuciferine and related aporphine alkaloids... 

Akuammine and related indole alkaloids annonaine, boldine, and related aporphine alkaloids berberine and related protoberberine alkalodis ergotamine, LSD, and related ergot alkaloids psUocybine, bufotenine, N,N-dimethyltryptamine, and related indoles harmahne and related beta-carbohne alkaloids kokusagine and related furoquinoUne alkaloids mescahne ibogaine and other monoterpene indole alkaloids... 

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-... 

Investigation of Xylopia descreta, a member of the Annonaceae family, has resulted in the isolation of four new protoberberine alkaloids— xylopinine, descretine, descretinine, and descretamine, in addition to the aporphine base, xylopine 49). 

T. sultanabadense Stapf., a small plant that grows under the shade of rocks on the rocky mountain slopes of eastern Turkey, is a source of the dimeric bisbenzylisoquinoline alkaloids thalbadensine, hemandezine, and thalictine, and the monomeric alkaloids thalifoline (isoquinolone), berberine (protoberberine), and magnoflorine (aporphine). 

The first part of this dissertation documents the isolation and identification of seven quaternary alkaloids from extracts of the roots of Thalictrum cultratum Wall., including six protoberberines (berberine, columbamine, jatrorrhizine, palmatine, (+)-thalidastine, and thalifendine) and one aporphine (magnoflorine). This research resulted in one publication [20]. 

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