Abstract
Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1–3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. Léonard. These ‘mixed’, constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1–3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range.
Highlights
We report on the isolation and structural elucidation of three new, structurally unique heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A [1], B [2], and C [3] (Fig. 1)
The new compounds 1–3, by contrast, are ‘mixed’, constitutionally unsymmetric dimers consisting of two monomeric parts that are – as for the michellamines – linked via C-6′ of both of the two naphthalene portions
LC-MS guided analysis of a crude leaf extract of A. ealaensis revealed the presence of further constituents, with MS profiles typical of dimeric naphthylisoquinoline alkaloids
Summary
Dieudonné Tshitenge Tshitenge, Doris Feineis, Virima Mudogo, Marcel Kaiser, Reto Brun4,5 & Gerhard Bringmann. Most remarkable is the ability of some Ancistrocladus species to produce dimers , giving rise to thrilling quateraryls with unique molecular architectures, possessing up to four stereocenters and three biaryl axes Some of these compounds show significant anti-HIV effects , while others exhibit pronounced activities against pathogens causing different tropical diseases like e.g., malaria . We report on the isolation and structural elucidation of three new, structurally unique heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A [1], B [2], and C [3] (Fig. 1) These secondary metabolites were isolated from the leaves of Ancistrocladus ealaensis Léonard , a Central African liana mainly occurring in the Northwestern part of the Democratic Republic of the Congo. The new ealapasamines A–C [1,2,3] were tested against the pathogens causing malaria tropica, leishmaniasis, Chagas’s disease, and African sleeping sickness, showing remarkably high activities against Plasmodium falciparum
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