Menispermaceae alkaloids isolated from

Fangchinoline (40), a 4> 5-benzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore (family Menispermaceae), was evaluated to possess significant antihyperglycemic activity studied in streptozotocin (STZ)-induced diabetic ddY mice in a dose-dependent manner the drug reduced the blood glucose level of diabetic mice by 52.7 6.7% when administered in 14 h-fasted diabetic mice at a dose of 1 mg/kg. Blood... 

The arrow poison curare, when produced from Chondrodendron species (Menispermaceae), contains principally the bis-benzyltetrahydroisoquino-line alkaloid tubocurarine (see page 324). Species of Strychnos, especially S. toxifera, are employed in making loganiaceous curare, and biologically active alkaloids isolated from such preparations have been identified as a series of toxiferines, e.g. C-toxiferine (Figure 6.85). The structures appear remarkably complex, but may be envisaged as a combination of two Wieland-Gumlich... 

The number of aporphine alkaloids isolated from plants is increasing exponentially. Kametani and Honda covers the chemistry of these compounds in detail [68]. Comprehensive reviews of aporphinoids, their molecular formula, structural formula, and spectral data have been published [69]. Their presence in South American Menispermaceae is represented by (+)-... 

Following the previous reviews published by Manske (1954), Jeffs (1967), and Bhakuni (1986), it is easy to see that the research on these alkaloids has grown substantially. This review covers the period from 1986 to 2001, and it shows that there were 589 citations describing studies on the phytochemistry and/or biological activities of 138 protoberberine alkaloids isolated from 310 plants from 13 families. Among the families cited as producers of protoberberine alkaloids, a simple analysis of Fig. 1, calls attention to the vast majority of citations from plants of the family Papaveraceae with 332 citations (45% of the total), followed by the family Berberidaceae with 144 citations (19%), and the family Ranunculaceae with 90 citations (12%). In terms of the number of different protoberberine alkaloids isolated from the families, again the family Papaveraceae comes in first place with 54 different alkaloids (39%), followed by the family Menispermaceae with 42 (30%), and the family Annonaceae with 36 (26%) different alkaloids. Chart 1 also shows that the families Apocynaceae, Fabaceae, Polygalaceae, and Rubiaceae each had only one alkaloid of this type described in the period. 

B. The Possible Common Origin of the Alkaloids Isolated from Plants of the Menispermaceae... 

Figure 1. Probable biosynthetic relationships between the different classes of alkaloids isolated from plants of the family Menispermaceae. The numbers in brackets are the numbers of alkaloids...

These alkaloids are present in several different plant families, with special emphasis in the mily Menispermaceae. 604 citations of bisbenzylisoquinoline alkaloids were discovered during this review. This represents 39.6% of the total number of alkaloids isolated from plants of the family. They have been found in 23 of the 45 genera studied, being more frequently found in Stephania (171), Cyclea (87), and Cocculus (63). Other plant families rich in Bis-BIQ are Ranunculaceae (Thalictnm), Beiberidaceae (Berberis, Mahania), Monimiaceae (Pcq>hnandra), Annonaceae (Phaeanthus, Popowia, Pseudoxandra, Rollinia, etc.) and Lauraceae. 

The chemical constituents of the roots of "Columba" (Jateorhiza pahnata Miers, = J. columba Miers) have been known for more then a century. Berberine was the first compound to be isolated, by Boedecker in 1849 (88). After that came columbamine, jatrorrhizine, and palmatine. It is very common to find this combination of alkaloids distributed in the various genera of the Menispermaceae. Also isolated from the genus was the dimer bisjatrorrhizine. In Dioscoreophyllum were found columbamine, jatrorrhizine and palmatine. 

The hasubanan alkaloids, a small group of alkaloids isolated from Stephania species of Menispermaceae, are structurally related to morphine. The hasubanan skeleton, however, is different from morphinan in that it contains a five-membered heterocyclic ring formed by linkage of the ethanamine nitrogen with C-14 instead of C-9. 

A detailed study of the alkaloidal content of the Formosan Stephania sasakii (Menispermaceae) has led to four new aporphines stesakine (4), dehydrostesakine (5), dehydrocrebanine (6),11 and dehydrophanostenine (7).4 Additionally, dehydro-stephanine (8) has been isolated from S. kwangsiensis.12... 

An isoquinoline system condensed to a tropolone is the skeleton for a tropoloisoquinoline alkaloid. The general structure of the five alkaloids of this type known so far are derivatives of the tautomers of 10-hydroxy-9H-azuleno[l,2,3-i,j]isoquinolin-9-one (42) and 9-hydroxy-10H-azuleno[l,2,3 i,j]isoquinoline-10-one (43) [88]. Recently, the first tropone-isquinoline alkaloid, pareitropone (44) has been isolated from the roots of the South American Menispermaceae, Cissampebs pareira [48]. 

The antimicrobial activity of aporphine alkaloids in general has been tested and oxoaporphines were the most active [108]. Some of these alkaloids are found to be toxic for mammalian cells in tissue cultures [109]. In another study of antimicrobial activity of fourteen benzylisoquinoline alkaloids, two oxoaporphines isolated from species of South American Menispermaceae, lysicamine (10) and O-methylmoschatoline (homomoschatoline) (11), had activity against cocci and gram positive bacilli, including Mycobacterium phlei [110]. 

There are only two alkaloids that constitute this small subgroup, but both bear an identical oxygenation pattern. Berbacolorflammine (218) is monoquatemary benzylisoquinoline at N-2, while caryolivine (281) has a tertiary nitrogen atom in a benzyisoquinoline system. Each alkaloid has only been isolated from a single plant, berbacolorflammine (218) from Pycnarrhena longifolia (Menispermaceae) and caryolivine (281) from Caryomene olivascens (Menispermaceae). 

There are only three alkaloids in this small subgroup, and all are derivatives of the monophenolic [C(12)], monosecondary [N(2)] alkaloid peinamine (71a) which has only been isolated from Abuta grisebachii (Menispermaceae). The other two alkaloids are 7-0-demethylpeinamine (60a) and N-methyl-7-O-demethylpeinamime (66b), both being metabolites of the same plant as above. In addition, the latter has been isolated from Pachygone dasycarpa (Menispermaceae). 

There are two alkaloids that are racemic mixtures cycleadrine (58) [(+/-) - fangchinoiine] from Cyclea barbaia and C. peltata (Menispermaceae) and (+/-)-tetrandrine (77) from the same two plants, as well as from Isopyrum thalictroides (Ranunculaceae) and Stephania hernandifolia (Menispermaceae). Menisidine (65) is likely a fangchinoiine isomer and menisine (66) is likely a (+)-tetrandrine stereoisomer. These latter two alkaloids were isolated from Stephania tetrandra (Menispermaceae). Oxofangchirine (349) is a benzyltetrahydoisoquinoline-benzylisoquinolone alkaloid from Stephania tetrandra (Menispermaceae). The stereochemistry at C( 1) is not defined. 

The only naturally occurring alkaloid of this small group is (+)-norcycleanine (124)[which is really 7 -O-demethylcycleanine). This alkaloid is not as widely distributed as its R,K diastereoisomer (-)-norcycleanine (125). The (+)-isomer has only been isolated from two plants Isolona hexaloba (Annonaceae) and Stephania cepharantha (Menispermaceae), neither of which are a source of the (-)-isomer (which was found in four Menispermaceous genera Chondodendron, Cyclea, Epinelrum, and Synclisia. The base tetra-O-demethylcycleanine (128a) has been reported, but data was not available. 

There are four alkaloids in the (-)-curine family (-)-curine (133), cycleacurine (134), O,O-dimethylcurine (135), and 12 -O-methyIcurine (140). These alkaloids differ in the position of various phenolic hydroxy groups and methoxy groups among the C(7), C(12), and C(6 ) positions. (-)-Curine (133) has been isolated from six genera of the Menispermaceae including Chondodendron, Cissampelos. Cyclea, Paracyclea, Pleogyne, and Stephania. In addition, this... 

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