Asymmetric synthesis and anti-protozoal activity of the 8,4′-oxyneolignans virolin, surinamensin and analogues

The asymmetric synthesis of 8,4′-oxyneolignans (−)-virolin, (−)-surinamensin and a number of analogues has been achieved. A divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate. In the 15 compounds that were tested, the level of substitution on the A-ring was found to directly influence the activity against Leishmania donovani whilst the activity against Plasmodium falciparum was influenced by numerous substitution and stereochemical factors.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Asymmetric synthesis of 8,4′-oxyneolignans achieved from lactate derived precursor. ► Synthesis allows easy variation of two key motifs. ► Anti-leishmanial activity dependant on level of A-ring substitution. ► Anti-malarial activity dependant on both substitution and stereochemical factors.