Spirombandakamine A₃ and Cyclombandakamines A₈ and A₉, Polycyclic Naphthylisoquinoline Dimers, with Antiprotozoal Activity, from a Congolese <i>Ancistrocladus</i> Plant

Abstract

Spirombandakamine A₃ (<b>7</b>) is only the third known naphthylisoquinoline dimer with a spiro-fused novel molecular framework and the first such representative to possess a relative <i>trans</i>-configuration at the two chiral centers in both tetrahydroisoquinoline subunits. It was found in the leaves of a botanically as yet unidentified Congolese <i>Ancistrocladus</i> plant, which is morphologically closely related to the Central African taxon <i>Ancistrocladus ealaensis</i>. Likewise isolated were the new cyclombandakamines A₈ (<b>8</b>) and A₉ (<b>9</b>), which belong to another most recently discovered type of unusual oxygen-bridged naphthylisoquinoline dimers and two previously described "open-chain" analogues, mbandakamines C (<b>10</b>) and D (<b>11</b>). 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 <b>7</b>-<b>9</b> displayed potent growth-inhibitory activity against <i>Plasmodium falciparum</i>, the protozoal pathogen causing malaria, and moderate effects on <i>Trypanosoma brucei rhodesiense</i>, the parasite responsible for African sleeping sickness.