Alkaloids from Ancistrocladaceae

Due to the brilliant, pioneering work by Govindachari and his colleagues at the CIBA Research Centre in Bombay, Ancistrocladus heyneanus Wall, is the most thoroughly investigated of all the Ancistrocladaceae. From the roots of this liana, a new alkaloid was isolated in nearly 1% yield, named ancistrocladine, and analyzed as C25H29O4N, as also confirmed by the mass spectrum (M = 407) 

The configuration at C-3 was demonstrated to be S by exhaustive ozonolysis of 1 to the known p-amino acid 3 (72). The relative configuration at C-1 compared with C-3 was shown to be trans by NMR methods, and the absolute configuration at the biphenyl linkage was elucidated by application of the exciton chirality method (13) on the fully aromatized chiral naphthyl isoquinoline 4 (72). The structure 1 thus deduced for ancistrocladine was later confirmed by X-ray analysis (72). 

From the same plant, 1,2-dehydro ancistrocladine (14), named an-cistrocladinine (for formula and data, see Table 1, Section II,F) (14), as well as 

O-methylancistrocladine (5) (75) were also isolated by Govindachari and coworkers and structurally determined. Besides this 5-1 type, the 7-l -coupled alkaloid ancistrocladisine (18) (76), and the 7-2 product ancistrocladidine (21) (77) were also found in A. heyneams and were completely elucidated (18) with all their chiral centers. The quality and reliability of this work can be judged from the fact that the two latter structures 18 and 21 were, much later (79), confirmed by X-ray analysis. 

Ancistrocladus hamatus (Vahl) Gilg is a related climber, found in Sri Lanka. Chemical investigation by Govindachari s group showed that this plant also contains ancistrocladine (1) as the major alkaloid, accompanied by its atrop-isomer, called hamatine (10). Compound 10, on dehydrogenation of its methyl ether, gives an aromatic isoquinoline, enantiomeric to 4, whereas ozonolysis yields the same p-amino acid 3, as ancistrocladine (1) (20,21). 

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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., F. Pokorny, H. Reuscher, D. Lisch, and L. A. Assi, Novel Ancistrocladaceae and Dioncophyllaceae type naphthylisoquinoline alkaloids from Ancistrocladus abbrevia-tus A phylogenetic link between the two families Planta Med-ica, 56, 496-497 (1990). 

Alkaloid from bark of Ancistrocladus tectorius (Ancistrocladaceae). 

Alkaloid from bark of A. tectorius (Ancistrocladaceae). Cryst. (MeOH/CH2Cl2). Mp 164°. 

Alkaloid from leaves and twigs of Ancistrocladus korupensis (Ancistrocladaceae). Shows antimalarial activity. Light brown solid. [a]p — 75.5 (c, 1.84 in MeOH). 

Quaternary alkaloid from +. korupensis (Ancistrocladaceae). Light yellow solid. [a]j, — 36 (c,... 

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],... 

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... 

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... 

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). 

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... 

Apart from this preliminary report, Triphyophyllum peltatum and Dioncho-phyllum tholonii are the only species outside the Ancistrocladaceae that contain naphthyl isoquinoline alkaloids. The characteristic biochemical difference, that... 

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