Aporphines dimerization

Acetylation of phenolic functions produces predictable effects on adjacent aromatic protons. For example, the assignment of the OH groups of thalictroga-mine (429) to C-l and C-7 was based on an upfield shift of H-ll and a downfield shift of H-8 in the diacetate (209). The NMR shifts of the C-8 hydrogen in several bisbenzylisoquinoline-aporphine dimers have been summarized (295). H-NMR spectra of some bisbenzylisoquinoline and related dimeric alkaloids have been tabulated (296,297). 

D. Umarova, S. Kh. Maekh, S. Yu. Yunusov, N. M. Zaitseva, S. A. Volkova, and P. G. Gorovoi, Khim. Prir. Soedin., 594 (1978) CA 90, 51406. Two unidentified bases, thought to be benzylisoquinoline-aporphine dimers (by UV, NMR, MS) were isolated in very small quantities from roots and rhizomes of T. sachalinense no physical properties were reported. 

Pronuciferine (1) has been synthesized by photocyclization of the brominated phenol (2).9a The light-induced rearrangement of proaporphines yields aporphines that are substituted at C-9 or at both C-8 and C-9.5 This topic is further discussed below, under the sections on aporphines and aporphine dimers. The known alkaloid N-methylcrotsparine has been found in Pachygone ovata.9b... 

The antitumor agent thalicarpine (114), a benzylisoquinoline-aporphine dimer, is metabolized by a series of microorganisms, but the only identified... 

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. 

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... 

The interesting alkaloid hernandaline (XCVI), which is intermediate between aporphines and benzylisoquinoline-aporphine dimers has been found in the related H. ovigera L. (33b). 

Benzylisoquinoline-aporphine dimers have been isolated from Thalictrum dioicum (pennsylvamine), T. revolutum (thalirevoline, thalirevolutine, thalilu-tine, and thalilutidine), and T. minus (thaliadamine). ... 

Thalicarpine was isolated from Cocculus laurifolius (73) in 1982. It is one of the rare examples of a tetrahydrobenzylisoquinoline-aporphine dimer. Thalicarpine seems to originate biogenetically from the oxidative coupling of two molecules of reticuline forming initially a Bis-BIQ. A second oxidative coupling, this one intramolecular, leads to the final product (Scheme 22). This alkaloid was also isolated from Thalictrum spp. (Ranunculaceae) and Hernandia ovigera (Hemandiaceae). 

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... 

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). 

H. Guinaudeau, M. Leboeuf, and A. Cave, J. Nat. Prod. 42, 133 (1979). Dimeric aporphine-benzylisoquinoline and aporphine-pavine alkaloids. Tabulates physical properties, sources, and references to synthesis of 28 alkaloids. 

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). 

M. Shamma and H. Guinaudeau, Tetrahedron 40, 479S (1984). Biosynthesis of aporphinoid alkaloids. In addition to monomeric alkaloids, discusses proaporphine- and aporphine-benzyliso-quinoline dimers, dimeric oxidized aporphines, and types derived by catabolism of benzyliso-quinoline-derived dimers. 

Irradiation with sunlight of pakistanamine (63), which is the only known pro-aporphine-benzylisoquinoline alkaloid, yields lumipakistanine (64), together with a trace amount of neolumipakistanine (65),5 while it is known that the acid-catalysed rearrangement of (63) takes a different course and generates the dimer (66) (Scheme 4).45... 

Dehydroglaucine and dehydronuciferine readily undergo C-7 to C-7 coupling, using mercuric acetate or nitrate to form the corresponding aporphine and dehy-droaporphine dimers.39 Nuciferine, which is 1,2-dimethoxyaporphine, can be hydroxylated at C-3 by the sequence (i) bromination in trifluoroacetic acid, (ii) metallation with phenyl-lithium, and (iii) oxidation with excess nitrobenzene.40... 

---