The "lactone concept" has been efficiently employed for the first atropo-enantioselective synthesis of knipholone and related natural phenylanthraquinones. Besides the regio- and stereoselective construction of the biaryl axis, another important step was the "synthetically late" introduction of the C-acetyl group, either by a Friedel-Crafts type acetylation or by an ortho-selective Fries rearrangement first tested on simplified model systems and subsequently applied to the highly atroposelective preparation of the natural products and of simplified analogs thereof for biotesting. The synthetic availability of these natural biaryls, their precursors, and their unnatural analogs permitted a broader investigation of the antiplasmodial activities of these interesting biaryls.

The aim of this study was to evaluate the antimicrobial activity of the crude extract of the twigs of Dorstenia barteri (DBT) as well as that of four of the five flavonoids isolated from this extract. Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and fungi (four species) were used. The agar disc diffusion test was used to determine the sensitivity of the tested samples while the well micro-dilution was used to determine the minimal inhibition concentrations (MIC) and the minimal microbicidal concentration (MMC) of the active samples. The results of the disc diffusion assay openUP (May 2008) showed that DBT, isobavachalcone (1), and kanzonol C (4) prevented the growth of all the 22 tested microbial species. Other compounds showed selective activity. The inhibitory activity of the most active compounds namely compounds 1 and 4 was noted on 86.4% of the tested microorganisms and that of 4-hydroxylonchocarpin (3) Abbreviations

BackgroundNatural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted.Experimental approachA current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski’s “Rule of Five” has been used to evaluate likely oral availability of the samples.ResultsA majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the “Rule of Five”. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed.Conclusions and implicationsThe p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.

phenylanthraquinone knipholone (1) and three of its natural derivatives as well as seven structurally related but simplified compounds have been examined for their antiplasmodial activity against asexual erythrocytic stages of two strains of Plasmodium falciparum in vitro (K1/chloroquine-resistant and NF 54/chloroquine-sensitive). All the phenylanthraquinones showed considerable activity with only little cytotoxicity, while their anthraquinone and phenyl moieties were completely inactive. Knipholone (1) and its natural derivatives can therefore be considered as a new group of potential antimalarials