Ancistrocladus isoquinoline alkaloids

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

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. 

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... 

Naphthyl Isoquinoline Alkaloids from Ancistrocladus Plants ... 

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-... 

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... 

MkheNamines. Atropisomeric dimeric naphthyl-(tetrahydro)isoquinoline alkaloids from the tropical lianas Ancistrocladus korupensis and A. abbreviatus. C46H48N2O8, Mr 756.89. 

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. 

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). 

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). 

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

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).

About 20 species of plant are known in the genus Ancistrocladus (Ancistro-cladaceae), which grows wild in the tropical areas of Asia, Malaysia, and West Africa. From this genus of plants, as well as two genera of the Dionchophyl-laceae family, naphthalene-isoquinoline-type alkaloids have been isolated. This type of alkaloid is quite rare, and only about 20 such alkaloids have been reported [1]. 

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