Ancistrocladus alkaloids

Table I summarizes the occurrence, the structures, and some physical data of Ancistrocladus alkaloids.

Beside the Ancistrocladaceae, only one other plant family so far has been found to produce naphthyl isoquinoline alkaloids (see also Section IV,B), the Dionchophyllaceae (31-33). Triphyophyllum peltatum (Hutch, et Dalz.) Airy Shaw is a large liana (34), endemic to the rain forests of West Africa. From the twigs of this plant, Bruneton and Cave isolated a new alkaloid, named tri-phyophylline (57), which, in contrast to all kno n Ancistrocladus alkaloids (see Section II), has only one oxygen function on the isoquinoline part of the molecule. No degradation reactions have been described for any of the Triphyophyllum alkaloids. Based exclusively on spectral evidence, triphyophylline was assigned the structure 23 (see Table II). The stereochemistry of the two... 

The published structures of Ancistrocladus alkaloids (see Section II) show a broad variation concerning the hydrogenation degree of the isoquinoline part, the... 

A possible biosynthetic route to acetogenin isoquinoline alkaloids is sketched in Scheme 3. According to this hypothesis (35,36), the common precursor to both molecular moieties of all the Ancistrocladus alkaloids could be the p-pentaketone 30 (or the corresponding P-polycarbonyl acid), which, for its part, would arise from six acetate units. Aldol-type condensation of 30 and aromatiza-... 

Scheme 18. Synthesis of the isoquinoline part of the Ancistrocladus alkaloid 15 54, 36).

Scheme 27. Asymmetric synthesis of optically active isoquinoline moieties of Ancistrocladus alkaloids (70).

The first naphthyl isoquinoline alkaloid to be synthesized in optically active form was ancistrocladine (1) itself, the most important and widespread of all the Ancistrocladus alkaloids (see Scheme 31). The effectivity of the ester bridge assisted aryl coupling method (as presented in Section V.D.) was demonstrated by the regioselective formation of the highly strained lactone 124, which— different from the corresponding triphyophylline precursor 108 (see Scheme... 

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. 

Two naphthalene-isoquinoline groups of alkaloids, ancistrocladidine (53) and ancistrotectorine (54), were isolated from Ancistrocladus heyneanus Wall [295], and A. tectorius (Lour.) Merr [296], respectively. The members of the plant family, ancistrocladaceae, are distributed in tropical Asia and Western Africa. Some are regarded as traditionally medicinal plants. The root of A. tectorius has been used to treat dysentery and malaria [296],... 

Yang et al. [118] reported the isolation and characterization of a novel naphthy-lisoquinoline alkaloid, ancisheynine (104) from the aerial part of Ancistrocladus heyneanus. The alkaloid is interesting in that it contains a previously undescribed N-2-C-8 linkage between the naphthyl and isoquinoline subunits, the presence of which was established with long-range correlation data. 

The dimeric stereoisomer alkaloids michellamines A, B and C (38) were obtained From the liane Ancistrocladus korupensis (Ancistrocladaceae). On the basis of their structural similarity to other PKC inhibitors, they have been studied for this activity. Michellamines inhibited rat brain PKC, with IC50 values in the 15-35 pM range. Michellamine B was a non-competitive PKC inhibitor with respect to ATP, whereas mixed-type inhibition was observed when the peptide concentration varied. The results indicate that the dimeric alkaloids bind to the PKC kinase domain and not to its regulatory domain. All three michellamines blocked both the ATP and the... 

Isoquinoline alkaloids Ancistrocladus abbreviatus CHCl3-MeOH-0.5% HBr (5 5 3) HSCCC... 

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). 

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... 

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. 

Structure-activity relationships indicate that the presence of a secondary amine function, and the absence of an oxygen substituent at C-6 and R-configuration at C-3 are important. Recently, a novel dimeric antiplasmodial naphthylisoquinoline alkaloid heterodimer, korundamine A (98), has been isolated from another species, Ancistrocladus korupensis belonging to the family Ancistrocladaceae that is biogenetically related to Dioncophyllaceae. Korundamide A is one of the most potent naturally occuring naphthylisoquinoline dimers... 

Naphthalenoisoquinolines.—A new base related to the unusual alkaloid (—)-ancistrocladine is (— )-ancistrocladinine (233), also found in Ancistrocladus heyneanus Wall. (Ancistrocladaceae), and which corresponds to ( —)-l,2-dehydroancistrocladine. " ... 

The unique substitution pattern of ancistrocladine (1), however, which was first isolated by Govindachari from the Indian liana Ancistrocladus heyneanus Wall. (Ancistrocladaceae) (4), can barely be brought into line with such a conventional isoquinoline biosynthesis. Its unprecedented structure, for which it was termed the most unusual of all the isoquinoline alkaloids (5), makes obvious that its biosynthesis must also differ from that of all other tetrahydroiso-quinoline alkaloids by starting not from aromatic amino acids, but from poly-ketide precursors, as first proposed by Govindachari (6). 

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