Naphthylisoquinoline alkaloid

Bringmann, G., Holenz, J., Assi, L. A., Zhao, C. and Hostettmann, K. 1996. Molluscicidal activity of naphthylisoquinoline alkaloids from Triphyophyllum and Ancistrocladus species. Planta Medica, 61 556-557. 

The or-naphthylisoquinoline alkaloids triphyophylline, isotriphyophylline, N-methyltriphyophylline, 8-O-methyltetradehydrotriphyophylline, and triphyo-peltine [assigned the structure (9 R — H) (cf Vol. 7, p. 107)] and its 5 -0-methyl ether (9 R = Me) have been isolated from Dioncophyllum thollonii.23... 

Further examples of the use of INADEQUATE in biosynthetic studies include biosynthesis of naphthylisoquinoline alkaloids,69 blepharismin C, toxic pigments of the ciliate Blepharisma japonicum,70 lambertellols A and B and lambertellin and metabolites of Ascomycete fungi.71... 

Naphthylisoquinoline alkaloids Ancistrocladus robertsoniorum CHCI3 MeOH-0.1 M HCl (5 5 3) HSCCC... 

The first enantioselective total synthesis of the 7,3 -linked naphthylisoquinoline alkaloid (-)-ancistrocladidine was accomplished by J.C. Morris and co-workers. The key steps of the synthesis were the Pinhey-Barton ortho-arylation and the Bischier-Napieralski cyclization. The natural product was isolated from the 1 1 mixture of atropisomers by recrystallization from toluene/petroleum ether. 

Bungard, C. J., Morris, J. C. First Total Synthesis of the 7,3 -Linked Naphthylisoquinoline Alkaloid Ancistrocladidine. Org, Lett, 2002, 4, 631-633. 

Compound 1 was the major alkaloid present and compounds 2 and 3 were previously unknown as natural products. The related naphthylisoquinoline alkaloids ancistrocladine (5) and its atropisomer hamatine (6) were previously known from other Asian Ancistrocladus species [25] while the 7,3 -linked naphthyl-isoquinoline, ancistrotectorine (8), has been previously isolated from Ancistrocladus lectorius from Thailand [26]. The structure of I was deduced from spectral data (UV, MS, NMR) as well as by its ready conversion to the known 2 through successive mesylation and LiAIH4 reduction. Likewise the structure and relative stereochemistry of 4 were established by spectral analysis (HMBC, NOESY) and by conversion to the known (-)-N-formyl-O-methylancistrocladine derivative 7 via successive formylation followed by methylation (Mel, NaH-DMF). 

Use of this method to form the extremely hindered biaryl linkage enabled completion of tlie first total synthesis of the rare 7,3 -linked naphthylisoquinoline alkaloid, ancistrocladidine (Scheme 13.21) [46]. 

A group of naphthylisoquinoline alkaloids has been identified of which twenty one have so far been isolated from Anois-trccladus and Tr-Lphyophyllwis pecies these being the 7-B-naphthylisoquinoline ancistrocladidine (10) and the 5 and 7 a-naphthyl-compounds listed in tables 4 and 5 respectively. 

Ancisheynin, a novel naphthylisoquinolinium alkaloid from Ancistrocladus heyneanus. Plants of the genera Ancistrocladaceae and Dinocophyllaceae are rich sources of naphthylisoquinoline alkaloids that vary in the degree of hydroxylation and 0-methylation. Butler and co-workers reported the isolation and structural characterization of a novel naphthylisoquinolinium alkaloid, ancisheynine (102) from Ancistrocladus heyneanus. The authors used long-range HMBC data to confirm the... 

Bringmann, G. and Rummey C. (2003) 3D QSAR investigations on antimalarial naphthylisoquinoline alkaloids by comparative molecular similarity indices analysis (CoMSIA), based on different alignment approaches. /. Chem. Inf. Comput. Sci., 43, 304-316. 

Stiefl, N., Bringmann, G., Rummey, C. and Baumann, K. (2003) Evaluation of extended parameter sets for the 3D-QSAR technique MaP implications for interpretability and model quality exemplified by antimalarially active naphthylisoquinoline alkaloids. /. Comput. Aid. Mol. Des., 17, 347-365. 

G., and Boyd, M. R. (1997) Michellamines D-F, new HlV-inhibitory dimeric naphthylisoquinoline alkaloids, and korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis. J Nat Prod. 60, 677-683. 

The plant families Ancistrocladaceae and Dioncophyllaceae are the only identifled sources of the unusual naphthylisoquinoline alkaloids (ref. 1). The family Ancistrocladaceae contains one genus, Ancistrocladus, which consists of approximately 20 species that are distributed in the Indian archipelago, tropical Asia and tropical West Africa. These isoquinoline alkaloids are structurally unique in that they appear to originate, biosynthetically, form the acetate-polymalonate pathway and not from amino acids (ref. 1). Another interesting structural feature of these compounds is that they exist as thermally stable atropisomers because of restricted rotation about the biaryl linkage. 

As mentioned, naphthylisoquinoline alkaloids are structurally unusual on account of the methyl group at the 3-position and oxygenation at the 8- and/or 6-position of the isoquinoline ring which points to a polyketide origin. This postulate has been supported by extensive studies conducted by Btingmann on the in vitro biomimetic synthesis of the naphthalene and isoquinoline portions of these compounds (ref. 13,14) and this work is worth briefly mentioning in a discussion on the total synthesis of these compounds. 

The first total synthesis of a naphthylisoquinoline alkaloid, the 7-1 linked O-methyltetradehydrotriphyophylline (55) isolated from the Dioncophyllaceae family (ref. 44), was reported in 1984 by Bringmann and coworkers (ref. 45). The requisite naphthalene 12 and isoquinoline 13 segments where available from biomimetic synthesis as previously detailed but attempted intermolecular coupling between the two moieties in their brominated forms under classical Ullmann type conditions (ref. 46) afforded only traces of the desired coupled product. Therefore, an intermolecular coupling approach utilising a temporary ether bridge was undertaken. 

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