Berberis Bisbenzylisoquinoline alkaloids

Bisbenzylisoquinoline alkaloids are dimeric benzyltetrahydroisoquinoline alkaloids that are known for their pharmacological activities. A well-described example is the muscle relaxant (+)-tubocurarine, which in crude form serves as an arrow poison for South American Indian tribes. In the biosynthesis of this broad class of dimeric alkaloids, it has been postulated that the mechanism of phenol coupling proceeds by generation of phenolate radicals followed by radical pairing to form either an inter- or intramolecular C - O or C - C bond. Enzyme studies on the formation of bisbenzylisoquinoline alkaloids indicated that a cytochrome P-450-dependent oxidase catalyzes C - O bound formation in the biosynthesis of berbamunine in Berberis cell suspension culture.15 This enzyme, berbamunine synthase (CYP80A1), is one of the few cytochromes P-450 that can be purified to... 

Aromoline and thalicberine have been isolated from Thalictrum lucidum,51 and berbamine and oxyacanthine from Berberis julianeae Schneid.52 The biosynthesis of bisbenzylisoquinoline alkaloids has been reviewed.53 An X-ray structure determination of ( + )-tubocurarine dibromide methanol solvate has been reported,54 and neuromuscular sensitivity to tubocurarine55 and the cardiovascular effects of the alkaloid56 have been further studied. Highly selective biological AT-demethylation of tetrandrine to iV(2 )-nortetrandrine by Streptomyces griseus has been described.29... 

Berbamunine (XXVI) (mp 190°-191°), a new bisbenzylisoquinoline alkaloid having a single diphenyl ether linkage, was isolated by Tomita and Kugo 16) from Berberis amurensis Rupr. 

Berberis cell cultures were also reported to produce bisbenzylisoquino-line alkaloids. Cassels et al. 412) screened 34 callus cell lines (33 species). In all cases the protoberberine alkaloid Jatrorrhizine was the major component in aU but 12 cell lines bisbenzylisoquinoline alkaloids were found. High levels of berbamine were found in B. angulosa (0.8% of dry weight) and B. henryana (0.48%). Berbamunine (16) and the new alkaloid 2-norberbamunine (17) were the major alkaloids in B. stolonifera cell lines... 

Berberis stolonifera 80A1 Berbamunine synthase Bisbenzylisoquinoline alkaloids Berbamunine [86]... 

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 title compounds, isolated from Berberis buxifolia Lam. (Berberidaceae), are the most recently reported of the eight known bisbenzylisoquinoline /V-oxide alkaloids. They are noteworthy in being the first N-oxides of this group to have their complete stereochemistry assigned by NMR NOEDS studies (see Section VI,A,2,b). Unfortunately, the first report (59) was based on an incorrect assignment due to overlap of the NMe and aliphatic signals of calafatine (88, Section... 

Several bisbenzylisoquinolines that are found in Berberis species of northern Pakistan can be derived, formally at least, from the naturally occurring spiro-dienone alkaloid pakistanamine (54).48 It is notable that the relative abundance of alkaloids derived by formal dienone-phenol rearrangement in (54) by mechanism (a) is greater than that of more hindered alkaloids formed by mechanism (b). 

Products of such oxidative fission of bisbenzylisoquinolines with one, two and three diphenyl ether linkages have been found to be natural products forming a small sub-group of secobisbenzylisoquinoline alkaloids. Those so far identified are karakoramine (68), jhelumine (69, R=H), chenabine (69, R=Me), sindamine (70), punjabine (73, R =H, R =CH0) and gilgi-tine (73, R =H, R =C00Me), isolated from Berberis lycium (J.E. Leet et al.. Heterocycles, 1982, J9, 2355 1983, 425),... 

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