Three new naphthylisoquinoline dimers,
jozibrevines A–C
(1a–c), were isolated from the West
African shrub Ancistrocladus abbreviatus, along with
the known dimer jozimine A2 (1d). The two
molecular moieties of 1a–d are coupled
via the sterically constrained 3′,3″-positions of their
two naphthalene units, so that the central biaryl linkage is rotationally
hindered. With the two outer axes also being chiral, 1a–d possess three consecutive stereogenic axes.
The four isolated dimers all have the same constitutions and identical
absolute configurations at the four stereogenic centers, but differ
by their axial chirality. They belong to the extremely small class
of Dioncophyllaceae-type naphthylisoquinoline dimers, i.e.,
being devoid of oxygen functions at C-6 and bearing the R-configuration at C-3 in their isoquinoline portions. Besides these
dimers, the plant produces predominantly typical Ancistrocladaceae-type
monomeric compounds, i.e., with the S-configuration
at C-3 and an oxygen function at C-6, such as the new ancistrobrevines
K (5) and L (6). Furthermore, a new hybrid-type
(i.e., mixed Ancistrocladaceae/Dioncophyllaceae-type) alkaloid was
identified, named ancistrobrevine M (7), which is 3R-configured and 6-oxygenated. Remarkable was the discovery
of its “inverse hybrid-type” counterpart, dioncoline
A (8). It is the as yet only known 3S-configured naphthylisoquinoline lacking an O-functionality
at C-6. The new jozibrevines A–C (1a–c) exhibited pronounced antiplasmodial activities in the submicromolar
range, with 1a being the most potent compound (IC50, 0.012 μM). Furthermore, jozimine A2 (1d) showed cytotoxicity against human colon carcinoma (HT-29),
fibrosarcoma (HT1080), and multiple myeloma (MM.1S) cancer cells,
displaying IC50 values of 12.0, 9.0, and 5.0 μM,
respectively, whereas jozibrevines A (1a) and B (1b) were nontoxic in this concentration range.