Laurent Aké Assi

On the structure of the dioncophyllaceae alkaloids dioncophylline a (“triphyophylline”) and “O-Methyl-Triphyophylline”

Abstract The naphthyl isoquinoline alkaloid “triphyophylline” is structurally re-investigated. The constitution, as well as the relative configurations at C-1 and C-3, are confirmed as published previously. “Triphyophylline” is found to be a stable rotational isomer with respect to the biaryl linkage, the absolute configuration at the stereogenic axis is determined to be S . The data of the natural product “ O -methyl-triphyophylline”, as reported in the literature, are shown not to be identical with those of the O -methylation product of triphyophylline, as prepared by partial synthesis. This inconsistency within the published series of Dioncophyllaceae alkaloids necessitates to rename “triphyophylline” (new name: “dioncophylline A”).

Activity of extracts and naphthylisoquinoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and A. barteri against Plasmodium falciparum in vitro

Abstract Five extracts from the tropical plant species Triphyophyllum peltatum, Ancistrocladus abbreviatus and A. barteri, and six pure naphthylisoquinoline alkaloids derived from these species have been examined for their antiplasmodial activity. These species are well-known in the traditional medicine of West Africa and are used for the treatment of fevers, malaria and other diseases. The extracts and alkaloids were tested against the asexual erythrocytic stages of two strains of Plasmodium falciparum in vitro (K1/chloroquine-resistant and NF 54/64, clone A1A9/ chloroquine-sensitive). Incorporation of 3H-hypoxanthine was measured in the presence of the test substances after 42 hr of incubation at 37°. All extracts and three alkaloids displayed activity. The two most potent compounds were dioncopeltine A and dioncophylline B. Structure-activity considerations indicate two possible criteria for antiplasmodial activity: an R-configuration at C-3 associated with the absence of an oxygen substituent at C-6 and the absence of N-methylation.

ancistrobrevine B, the first naphthylisoquinoline alkaloid with A 5,8′-coupling site, and related compounds from Ancistrocladus abbreviatus

Abstract The isolation of ancistrobrevine B, a new naphthylisoquinoline alkaloid from Ancistrocladus abbreviatus , is described. Elucidation of the complete structure, including the absolute configuration at the two stereogenic centres and the axis, was achieved by chemical and spectroscopic methods. Ancistrobrevine B exhibits a hitherto unprecedented 5,8′-coupling type. The known alkaloids ancistrocladine, hamatine and dioncophylline A were also isolated for the first time from this species.

Dioncophylline C from the roots of Triphyophyllum peltatum, the first 5,1′-coupled dioncophyllaceae alkaloid

Abstract A new naphthylisoquinoline alkaloid, named dioncophylline C, was isolated from the roots. of Triphyophyllum peltatum . Its complete stereostructure was established by spectroscopic, chiroptical, and chemical methods. Dioncophylline C is the first 5,1′-linked Dioncophyllaceae alkaloid; this coupling type has hitherto been found only for Ancistrocladaceae alkaloids, yet with a different stereochemistry and a higher oxygenation degree.

Dioncopeltine A and dioncolactone A: Alkaloids from Triphyophyllum peltatum☆

Abstract The isolation of two novel alkaloids from Triphyophyllum peltatum is described. The complete stereostructure of dioncopeltine A, which is closely related to dioncophylline A, is established by spectroscopic, chiroptical, and degradative methods, and is furthermore confirmed by its transformation to O-methyl-dioncopophylline A, as well as by X-ray crystallography. Dioncolactone A, which can be transformed into dioncopeltine A by reductive ring-opening, is the first naturally occurring representative of this novel type of ‘axially prostereogenic’ biaryl alkaloids.

Dioncophylline B, a naphthylisoquinoline alkaloid with a new coupling type fromTriphyophyllum peltatum

Abstract The isolation of a new alkaloid, dioncophylline B, from the roots of Triphyophyllum peltatum is described. Its complete structure, including absolute configuration, was established by spectroscopic and degradative methods. Dioncophylline B has an unprecedented 7,6′-coupling, and is, because of the lack of bulky substituents next to its axis, the first ‘non-bridged’ naphthylisoquinoline alkaloid that is not split up into stable atropisomers.

Droserone from cell cultures of Triphyophyllum peltatum (Dioncophyllaceae) and its biosynthetic origin.

The growth and droserone content of callus cultures of Triphyophyllum peltatum grown in liquid 1/5 Linsmaier and Skoog medium was studied. During a lag phase in growth, droserone concentrations in the medium reached a value of 2.1 mg g-1 fr. wt. After this maximum value the concentration decreased slightly to 1.8 mg g-1 fr. wt., while the growth of the calli was enhanced (25% increase in fr. wt. within 7 days). Plumbagin and isoshinanolone were likewise present in the medium. By feeding 13C2-labelled acetate to the cultures the biosynthesis of droserone was elucidated. The incorporation of whole C2-units unambiguously shows its acetogenic origin and fits well in the biosynthetic scheme suggested for the structurally--and biogenetically--related naphthylisoquinoline alkaloids.

Habropetaline A, an antimalarial naphthylisoquinoline alkaloid from Triphyophyllum peltatum.

The isolation, structural elucidation, and antiprotozoal activities of habropetaline A, a novel naphthylisoquinoline alkaloid from Triphyophyllum peltatum, are described. This alkaloid had previously only been identified on line, by the LC-MS/MS-NMR-CD triad, in the crude extract of the rare and difficult-to-provide related plant species Habropetalum dawei, whose small quantities available had not permitted to isolate the compound. As predicted by quantitative structure-activity relationship (QSAR) investigations, habropetaline A exhibits strong antimalarial activity against Plasmodium falciparum, while it is inactive against other protozoal pathogens (Trypanosoma brucei rhodesience, T. cruzi, and Leishmania donovani).

Atrop-diastereomer separation by racemate resolution techniques: N-methyl-dioncophylline A and its 7-epimer from Ancistrocladus abbreviatus

Abstract The isolation of N -methyl-dioncophylline A and N -methyl-7- epi -dioncophylline A from Ancistrocladus abbreviatus is described. Atrop-diastereomer resolution was achieved analytically on a chiral chromatographic phase, and preparatively after esterification with a chiral carboxylic acid. Structural elucidation assisted by partial synthesis is reported and chemotaxonomic implications of this first isolation of Dioncophyllaceae alkaloids from an Ancistrocladus species are discussed.

Differential sensitivity of erythrocytic stages of the rodent malaria parasite Plasmodium chabaudi chabaudi to dioncophylline B, a highly active naphthylisoquinoline alkaloid

Abstract Four-week-old OF1 mice, infected with synchronized Plasmodium chabaudi chabaudi blood forms, were intraperitoneally injected with the naphthylisoquinoline alkaloid dioncophylline B (10 mg kg−1 day−1) at three consecutive days. The respective groups were treated when rings, trophozoites, and schizonts were predominant. Microscopical observations of thin blood smears were made every two hours after the start of the experiment. A clear dependency of the effectiveness of dioncophylline B treatments on the timing of drug administration was demonstrated. Based upon the evolution of total parasitaemia and the survival rates, it was concluded that ring stages are insensitive to dioncophylline B, while the drug is highly effective when given at the trophozoite stage and partially effective when given at the schizont stage. Dioncophylline B seems to act by inhibiting the haemozoin degradation, as indicated by pigment clumping, and by impairing the segmentation of schizonts.