Spirombandakamine A3 and Cyclombandakamines
A8 and A9, Polycyclic Naphthylisoquinoline Dimers,
with Antiprotozoal Activity, from a Congolese Ancistrocladus Plant
posted on 2021-04-12, 15:06authored byBlaise
Kimbadi Lombe, Doris Feineis, Virima Mudogo, Marcel Kaiser, Gerhard Bringmann
Spirombandakamine A3 (7) is only the third
known naphthylisoquinoline dimer with a spiro-fused novel molecular
framework and the first such representative to possess a relative trans-configuration at the two chiral centers in both tetrahydroisoquinoline
subunits. It was found in the leaves of a botanically as yet unidentified
Congolese Ancistrocladus plant, which is morphologically
closely related to the Central African taxon Ancistrocladus
ealaensis. Likewise isolated were the new cyclombandakamines
A8 (8) and A9 (9),
which belong to another most recently discovered type of unusual oxygen-bridged
naphthylisoquinoline dimers and two previously described “open-chain”
analogues, mbandakamines C (10) and D (11). The full absolute stereostructures of these compounds were assigned
by combining spectroscopic, chemical, and chiroptical methods. Preliminary
biomimetic investigations indicated that both spirombandakamine- and
cyclombandakamine-type dimers result from the oxidation of their open-chain
mbandakamine-type congeners. The new dimeric alkaloids 7–9 displayed potent growth-inhibitory activity
against Plasmodium falciparum, the protozoal pathogen
causing malaria, and moderate effects on Trypanosoma brucei
rhodesiense, the parasite responsible for African sleeping
sickness.