Antileukemic ancistrobenomine B and related 5,1'-coupled naphthylisoquinoline alkaloids from the Chinese liana Ancistrocladus tectorius.

A striking feature of the metabolite pattern of the Southeast Asian liana Ancistrocladus tectorius (Ancistrocladaceae) is the predominance of 5,1'-coupled naphthylisoquinoline alkaloids. About 20 alkaloids of this coupling type have so far been discovered in this plant species. Here, we report on the isolation of four new 5,1'-linked naphthylisoquinolines from the twigs and stems of A. tectorius. Two of them, the ancistrobenomines B (5) and C (6), belong to the very rare group of alkaloids with a fully dehydrogenated isoquinoline portion. Likewise unusual for naphthylisoquinoline alkaloids is the presence of a hydroxymethylene group at C-3. Within the large class of meanwhile ca. 180 such natural products, this structural peculiarity had so far been known only from two other representatives isolated from the Malaysian species A. benomensis, and from one single naphthalene-devoid 3-hydroxymethyleneisoquinoline from A. tectorius. Seven further 5,1'-linked alkaloids, previously isolated from related Asian and African Ancistrocladus species, have now been identified for the first time in A. tectorius. Their structural elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and chiroptical (electronic circular dichroism) methods. Ancistrobenomine B (5) exhibited moderate effects against Plasmodium falciparum and Trypanosoma brucei rhodesiense in vitro, and it was found to display strong cytotoxic activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000.

Ancistectorine D, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8'- and 7,1'-linked metabolites from the Chinese liana Ancistrocladus tectorius.

From the twigs and stems of the Chinese liana Ancistrocladus tectorius (Ancistrocladaceae), two new 5,8'-coupled naphthylisoquinolines, ancistectorine D (5) and its 6-O-demethyl derivative 6, were isolated, along with two new 7,1'-linked alkaloids, 6-O-methylancistectorine B1 (7) and ancistectorine B2 (8). Two further compounds, ancistroealaine A (4) and 6-O-demethyl-8-O-methyl-7-epi-ancistrobrevine D (10), already known from related Asian and African Ancistrocladus species, were discovered for the first time in A. tectorius. The structure elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and chiroptical (circular dichroism) methods. Chemotaxonomically remarkable, 5,8'-coupled naphthylisoquinolines have as yet been found quite rarely in Asian Ancistrocladus species, where only two examples have so far been detected, while alkaloids with this coupling type represent the by far the largest group of constituents in African taxa. Ancistectorine D (5) shows promising activities against the protozoan parasites Trypanosoma cruzi and Leishmania donovani, and it was likewise found to display strong cytotoxic activities against human leukemia (CCRF-CEM) and multidrug-resistant tumor cells (CEM/ADR5000).

Axially Chiral Dimeric Naphthalene and Naphthoquinone Metabolites, from Root Cultures of the West African Liana Triphyophyllum peltatum.

Root cultures of the West African liana Triphyophyllum peltatum were initiated from stem explants of in vitro cultivated shoots. From these organ cultures, three new binaphthalenes, one binaphthoquinone, and two (bi)naphthalene glucosides were isolated, with substitution patterns related to those of the naphthylisoquinoline alkaloids, which are the "normal" main metabolites of T. peltatum. The structures of the diglucoside dioncoquinoside A (1) and of the axially chiral biaryls triphyoquinols A1 (3), A2 (4), and B (5), triphyoquinoside A (6), and triphyoquinone A (7) were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and by application of electronic circular dichroism (ECD) spectroscopy in combination with the exciton chirality method and quantum-chemical ECD calculations. The root cultures likewise produced the known alkaloids dioncophylline A (8), 5'-O-demethyldioncophylline A (9), dioncopeltine A (10), habropetaline A (11), and 5'-O-methyldioncophylline D (12a/b), the naphthalene glucoside plumbaside A (2), and the naphthoquinones plumbagin (13), droserone (14), and 8-hydroxydroserone (15).

Ancistrotectoquinones A and B, the First Quinoid Naphthylisoquinoline Alkaloids, from the Chinese Liana Ancistrocladus tectorius.

From the leaves and stems of Ancistrocladus tectorius (Ancistrocladaceae) from the Chinese island Hainan, two novel-type 7,3'-coupled naphthylisoquinolines, named ancistrotectoquinones A (4) and B (5), were isolated. They are the first alkaloids with a 1,4-naphthoquinone portion coupled to an isoquinoline moiety. Due to the lowered degree of steric hindrance next to the biaryl axis and for electronic reasons, 4 and 5 occur as pairs of configurationally semi-stable, and, thus slowly interconverting atropo-diastereomers. The Gibbs free energies of activation between the two atropisomers of ancistrotectoquinone A (4a/b) were determined by measuring the time-dependent decrease of diastereomeric purity of freshly separated samples enriched with the M- or P-atropisomer and, computationally, by DFT calculations. The absolute configurations at the biaryl axes of the atropo-diastereomers of 4a/b and 5a/b were assigned by online LC-CD analysis. The stereostructure of 4a/b was further confirmed by its semi-synthesis from the likewise 7,3'-coupled 'normal' naphthylisoquinoline alkaloid ancistrotectorine (6), by biomimetic oxidation with Fremy's salt.