The Aporphine-Benzylisoquinoline Dimers

The second dimeric base, (—)-pennsylpavoline (179), was shown to correspond to C-l-demethylpennsylpavine. Specifically, its NMR spectrum was devoid of the 8 3.71 singlet which represents the C-1 methoxyl absorption in (—)-pennsylpavine (178). Evaluation of CD spectra of these novel dimers and comparison with those of the aporphine (+)-A -methyllaurotetanine and the pavine (—)-platycerine led to the assignment of the absolute configurations as depicted in expressions 178 and 179. These dimers are probably derived biosynthetically from the aporphine-benzylisoquinoline dimers, (-)-pennsylvanine and (-)-pennsylvanamine, which were found in the same plant (7,173). 

Berberis actinacantha Mart, ex Schult. (Berberidaceae) furnished (+)-epiberbivaldine (475), C36H3gN206, amorphous, [ot] 5 +45.7° (c 0.12, CHC13). Epiberbivaldine is di-astereomeric to the known berbivaldine (89). Structure proof was by NOEDS and di-enone-phenol rearrangement to an aporphine-benzylisoquinoline dimer (556). 

Natalinine (491), C25H23N05, amorphous, is a minor alkaloid of Berberis empetrifolia Lam. MS and high-resolution NMR established the skeletal structure, and CD indicated the (R) configuration (561). Natalinine may be derived biogenetically from catabolism of an aporphine-benzylisoquinoline dimer [such as pakistanine (92), a major co-occurring alkaloid] (561), or by rearrangement of a coyhaiquine (107)-type dimer (562). 

Northalicarpine (498), C40H46N2Og, from Hernandia peltata Meissner, was identified by MS and FT NMR. It is the first nor aporphine-benzylisoquinoline dimer demethylated on the aporphine (rather than the benzylisoquinoline) nitrogen (549). 

Thalifasine (516), C40H46N2O9, [a] [67.9° (c 0.80, MeOH), is the last of the six 12 —8 ether-linked aporphine-benzylisoquinoline dimers (the others being 302,304,473, 514, and 515) isolated from Thalictrum faberi. The UV base shift of the alkaloid and a NMR study of its O, O-diacetate suggested the indicated location of the hydroxy substituents. The CD curve, closely resembling that of thalifaberine (302), indicated the same configuration (545). 

All aporphine-benzylisoquinoline dimers so far isolated from Thalictrum species have identical configurations, suggesting common biogenesis (545). Rules for predicting the configurations of Thalictrum bisbenzylisoquinoline alkaloids have been derived the sole exception is isothalidezine (170), which may be formed by epimerization via an iminium salt of the major co-occurring alkaloid thalidezine (53) (538). 

The year under review has witnessed the isolation and structural elucidation of no less than nine new aporphines, as well as of five aporphine-benzylisoquinoline dimers. Two of these five aporphine-benzylisoquinolines, namely kalashine and khyberine, are the first such dimers known to be substituted at C-l 1 of the aporphine moiety. Thallium(m) trifluoroacetate is an oxidizing agent which effects the cyclization of tetrahydrobenzylisoquinolines to aporphines in satisfactory yields.1 A listing of aporphinoid alkaloids has appeared.2... 

A study of three Berberis species, namely B. orthobotrys, B. calliobotrys, and B. zabeliana, has yielded four new aporphine dimers, i.e. chitraline (56), 1-O-methylpakistanine (57),67,68 kalashine (58),68,69 and khyberine (59).70 Kalashine and khyberine are the first aporphine-benzylisoquinoline dimers incorporating a diaryl ether terminal at C-ll of the aporphine moiety. 

A practical route to aporphine-benzylisoquinoline dimers by an improved Ullmann diphenyl ether synthesis has been worked out. The aromatic halide and the phenolic compound are heated with pentafluorophenyl copper in dry pyridine the average yield of dimer being 50%. ... 

Fourteen alkaloids were isolated from extracts of the whole plant of ThaUctrum fauriei Hayata, among which were seven alkaloids of novel structure including three aporphines (3-0-demethyloconovine, faurine, and O-methylfaurine), three aporphine-benzylisoquinoline dimers (fauridine, faurithaline, and 3-methoxyfaurithaline), and one aporphine-pavine dimer (fauripavine). Alkaloids of previously established structure that were isolated and identified included five aporphines (corydine, isocorydine, isooconovine, oconovine, and thalisopynine), and two morphinans (ocobotrine and pallidine). 

Thalifaboramine is but one of over 16 new aporphine-benzylisoquinoline dimeric alkaloids that have been isolated from Thalictrum faberi Ulbr., and the crude basic fraction, as well as most of the new alkaloids, including thalifaboramine (79), have demonstrated cytotoxic effects against the P-388 carcinoma cell [133],... 

Thalifarazine (10), C40H4iOlN2 (682.3254), [a]D +72° (c 0.06, MeOH), was isolated along with eleven other aporphine-benzylisoquinoline dimeric alkaloids from an extract (EtOH) of the whole plant of T. cultratum Wall, in 1986 [2,4], The UV spectrum of this phenolic alkaloid was similar to those of other aporphine-benzylisoquinoline dimers and displayed maxima at 228 nm (log e 4.70), 270 (shX4.29), 283 (4.38), 297 (shX4.25), and 310 (shX4.02)while the CD spectrum... 

A continuing investigation of the alkaloids of Thalictrum polygamum Muhl. has resulted in the isolation of members of an interesting and novel isoquinoline group, the aporphine-pavine dimers. Pennsylpavine (59) and pennsylpavoline (60) are weakly basic phenolic alkaloids which are accompanied in the plant by the aporphine-benzylisoquinolines pennsylvanine (46) and pennsylvanamine (47). It therefore seems likely that (46) and (47) are biogenetic precursors for (59) and (60), respectively. ... 

Benzylisoquinolines.—An extensive review of Thalictrum alkaloids has appeared. These include benzylisoquinolines, bisbenzylisoquinolines, isoquinolones, apor-phines, aporphine-benzylisoquinoline dimers, phenanthrenes, protoberberines, protopines, pa vines, and isopa vines. The alkaloids of the Lauraceae have also... 

Proaporphine-BeHzylisoquinoline Dimers.—The first known proaporphine-benzylisoquinoline dimer, pakistanamine (112), has been isolated from Berber is baluchistanica Ahrendt (Berberidaceae). Dienone-phenol rearrangement of pakistanamine (112) using dilute hydrochloric acid gave rise to the phenolic aporphine-benzylisoquinoline dimer (113), and O-methylation of this product with diazomethane provided 00-dimethylpakistanine (114) of known structure and stereochemistry. ... 

Aporphine-Benzylisoquinoline Dimers.—The known aporphine-benzylisoquinoline dimer (-f-)-thalicarpine (116) has been found in Hernandia ovigera L. 

A relevant and very recent development is the isolation and characterization by Beal, Doskotch, and co-workers, of the new alkaloid ( + )-thaliadine from Thalictrum minus L. race B (Ranunculaceae). This alkaloid is accompanied in the plant by such aporphine-benzylisoquinoline dimers as (-h)-adiantifoline, (+)-desmethyladiantifoline, and (-h)-thaliadanine (Sec. 12.1), and must be formed from their oxidative degradation. ... 

Among the isoquinoline alkaloids, the aporphine-benzylisoquinolines had been considered a terminal stage of anabolic development in the biogenetic tree. The discovery of pennsylpavine and pennsylpavoline, two examples of a new group of dimeric alkaloids, the aporphine-pavines, has extended the biogenetic locus, since they are probably derived from aporphine-benzylisoquino-line dimers. 

The following secodimeric alkaloids have been isolated from natural sources (+)-hernandaline (197), from Hernandia ovigera L. (158), (—)-natalinine (198) (759), and (+)-coyhaiquine (199) (160), the two latter from Berberis empetrifolia Lam. with the yields 0.00005 and 0.00008%, respectively. Appropriate aporphine-benzylisoquinoline or proaporphine-benzylisoqui-noline dimers are probably precursors of these seco alkaloids, although... 

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