Addition of thiols to o-quinone methide: New 2-hydroxy-3-phenylsulfanylmethyl[1,4]naphthoquinones and their activity against the human malaria parasite Plasmodium falciparum (3D7)

A series of 36 new phenylsulfanylmethyl[1,4]naphthoquinones (7–42) were synthesized by a three-component reaction that involves lawsone, the appropriate aldehyde and thiols with variable substitution patterns. These reactions involve the in situ generation of o-quinone methides (o-QM) via Knoevenagel condensation and 1,4-nucleophilic addition under conventional heating or microwave irradiation. The new naphthoquinones obtained by this methodology were shown to have moderate to good in vitro antimalarial activity against Plasmodium falciparum (3D7).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We synthesized a series of 36 new phenylsulfanylmethyl-[1,4]-naphthoquinones by a three-component reaction. ► These reactions involve the in situ generation of o-quinone methides (o-QM) via Knoevenagel condensation. ► The naphthoquinones prepared shown to have moderate to good in vitro antimalarial activity.