Benzophenanthridine

X-ray crystal structure, 6, 516 Benzophenanthridines synthesis from anils, 2, 416 Benzophenanthridines, tetrahydro-synthesis, 2, 469 Benzo[c]phenanthridines synthesis, 2, 414 from aryl isocyanides, 2, 411 from benzynes, 2, 432 Benzo[i]phenanthridines synthesis, 2, 414 Benzophenanthridinones... 

Das S (2000) Biophysical studies on the interaction of benzophenanthridine alkaloids with polymorphic nucleic acid structures. PhD Thesis, Jadavpim University... 

The 6,7-secoberbine alkaloids contain the four following natural products corydalic acid methyl ester (55), corydamine (56), N-formylcorydamine (57), and hypecumine (58). These bases, called 3-arylisoquinolines, were described by Shamma and Moniot (2) as a separate class of isoquinoline alkaloids. Santavy (7) classified them among benzophenanthridines. It seems, however, that they may be considered as biosynthetic intermediates between the protoberberines on the one hand and the benzophenanthridines on the other. 

It was postulated (169) that these amides are 8,8a-secobenzophenanthridine alkaloids produced by oxidative cleavage of ring B of the corresponding benzophenanthridines. The success of Baeyer-Villiger-type oxidations of the immonium bond of benzophenanthridine skeletons (168,171,172,175) indicates that this type of oxidation could be a real biological pathway. 

DITTRICH, H., KUTCHAN, T.M., Molecular cloning, expression, and induction of berberine bridge enzyme, an enzyme essential to the formation of benzophenanthridine alkaloids in the response of plants to pathogenic attack, Proc. Natl. Acad. Sci. USA, 1991,88, 9969-9973. 

KUTCHAN, T.M., DITTRICH, H., Characterization and mechanism of the berberine bridge enzyme, a covalently flavinylated oxidase of benzophenanthridine alkaloid biosynthesis in plants, J. Biol. Chem., 1995,270,24475-24481. 

VavreCkova, C., Gawlik, I. and MUller, K. 1996. Benzophenanthridine alkaloids of Chelidonium majus. I. Inhibition of 5- and 12-lipoxygenase by a non-redox mechanism. Planta Medica, 62 397-401. 

Dupont, C., Couillerot, E., Gillet, R., Caron, C., Zeches-Hanrot, M., Riou, J.-F. and Trentesaux, Ch. 2005. The benzophenanthridine alkaloid fagaronine induces erythroleukemic cell differentiation by gene activation. Planta Medica, 71 489 94. 

Chen, J.-J., Fang, H.-Y., Duh, Ch.-Y. and Chen, I.-S. 2005. New indolopyrido-quinazoline, benzophenanthridines and cytotoxic constiments from Zanthoxylum integrifolium. Planta Medica, 71 470 75. 

Lenfeld, J., Kroutil, M., Marsalek, E., Slavik, J Preininger, V. and Simanek, V. 1981. Anti-inflammatory activity of quaternary benzophenanthridine alkaloids from Chelidonium majus. Planta Medica, 43 161-165. 

Villegas, M., Leon, R. and Brodelius P. E. 1999. Effects of alginate and immobilization by entrapment in alginate on benzophenanthridine alkaloid production in cell suspension cultures of Eschscholtzia californica. Biotechnology Letters, 21(1) 49-55. 

Pyrolysis of anils has long been known to give polycycles, as shown by the synthesis of phenanthridine (120) (1889CB3340) and of the two benzophenanthridines (121) and (122) <1891LA(266)155>. More recently, quinoline has been obtained by flash vacuum pyrolysis of the dianil (123) <80JCS(P1)2200). 

Figure 1. Gas chromatogram of PAH in a work atmosphere a, particulate PAH b, gaseous PAH. The peak identities are 1, naphthalene 2, 2-methylnaphthalene 3, 1 -methylnaphthalene 4, biphenyl 5, acenaphthene 6, dibenzofuran 7, fluorene 8, 2-methylfluorene 9, 1-methylfluorene 10, dibenzothiophene 11, phenanthrene 12, anthracene 13, methylphenanthrene/methylanthracene 14, methylphenan-threne/methylanthracene 15, 2-methylanthracene 16, 4,5-methylenephenanthrene 17, methylphenanthrene/methylanthracene 18,1-methylphenanthrene 19, fluoranthene 20, benzo(def)dibenzothiophene 21, pyrene 22, ethylmethylenephena-threne 23, benzo(a)fluorene 24, benzofb)fluorene 25, 4-methylpyrene 26, meth-ylpyrene 27, 1-methylpyrene 28, benzothionaphthene 29, benzo(c)phenanthrene 30, benzophenanthridine 31, benzo(2i)anthracene 32, chrysene/triphenylene 33, benzo(b)fluoranthene 34, benzof])fluoranthene 35, benzo(k)fluoranthene 36, ben-zo(c)pyrene 37, benzofa)pyrene 38, perylene 39, indenof 1,2,3-cd)pyrene 40, dibenz(a, /a,h)anthracenes 41, benzofghi)perylene 42, anthanthrene 43, coro-...

Sanguinarine 1 is the prototype of benzophenanthridine alkaloids which occur frequently in plants of the family Papaveraceae. It has anticancer activity and has become of commercial interest because of its antibacterial properties. It is known from biosynthetic studies that protopine 2 is a metabolite on the pathway to sanguinarine, and recent work has shown that a microsomal cytochrome P-450 NADPH dependent enzyme will hydroxylate protopine... 

During synthetic studies on the benzophenanthridine alkaloids, the nitrile ester 1 was treated with sodium hydride in THF in the expectation that a Thorpe-Dieckmann type of reaction would... 

The benzo[ a Jphenanthridine ring system resembles the structure of chrysene, another carcinogen. It is intriguing to note that the carcinogenicity of chrysene is drastically increased by the addition of a methyl group at position 5 of that molecule [86-90]. The position of this methyl group (see structure 9) corresponds to that in the aforementioned benzophenanthridine alkaloids. 

The structural elucidation of a new benzophenanthridine alkaloid, luguine (100) was reported (61) in which the 13C spectrum confirmed both the aromatic nature of ring B and the presence of a hydroxyl group at C-11. The spectrum showed four aliphatic carbon resonances and these were assigned by off-resonance decoupling. 

Badger and Sasse have described the preparation of 2-, 3-, and 8-bromophenanthridine by the cyclization of the appropriate bromo-formamidobiphenyl with polyphosphoric acid.25 In the case of 2-bromo-2 -formamidobiphenyl a higher concentration of phosphorus pentoxide in the acid was necessary to effect ring closure, and a simple steric effect was invoked.26 Nevertheless, the Morgan-Walls reaction has been used to obtain several overcrowded compounds in which unfavorable steric factors operate. Following the original report of the preparation of the 1,10-dimethylphenanthridine (5a) by this procedure,27 several other examples have been described, notably the synthesis of the related phenanthridine (5b),28 the l,2-(6)29 and 9,10-benzophenanthridines (7),30 and the 1,2 9,10-dibenzophenanthridine (8).29... 

The Morgan-Walls cyclization has also been employed in eases where the acylamino group is attached to a reduced ring. For example, the amides (13a-c,41 and d42) are readily cyclized by phosphoryl chloride and the tetrahydro-l,2-benzophenanthridine (14) has been prepared... 

The ferrous oxalate procedure has been employed successfully to prepare 8,10-dimethyl-3,4-benzophenanthridine from 2-mesityl-l-nitronaphthalene.85 However, an attempted preparation of 4,9-diazachrysene from 2,2 -dimethyl-6,6/-dinitrobiphenyl failed, while treatment with an excess of triethyl phosphite gave 1,10-dimethyl -benzo[c]cinnoline (11%) as the only recognizable product. Failure... 

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