naphthoquinones and quinone-methide

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).

Topics: Antimalarials; Cells, Cultured; Flow Cytometry; Humans; Indolequinones; Malaria, Falciparum; Molecular Structure; Naphthoquinones; Plasmodium falciparum; Sulfhydryl Compounds

A new mild method has been devised for generating o-(naphtho)quinone methides via fluoride-induced desilylation of silyl derivatives of o-hydroxybenzyl(or 1-naphthylmethyl) nitrate. The reactive o-(naphtho)quinone methide intermediates were trapped by C, O, N, and S nucleophiles and underwent "inverse electron-demand" hetero-Diels-Alder reaction with dienophiles to give stable adducts. The method has useful potential application in natural product synthesis and drug research.

Topics: Dimerization; Indolequinones; Molecular Structure; Naphthoquinones; Time Factors

Treatment of benzannulated enediynyl alcohols with trifluoroacetic acid at room temperature promoted a cascade sequence of cyclization reactions, leading to 1,4-naphthoquinone methides. The transformation involved an unusual two-carbon ring expansion from the cyclic alcohols and the construction of the p-quinone methide ring from an acyclic system along the reaction pathway.

Topics: Acids; Alcohols; Benzene; Catalysis; Cyclization; Enediynes; Indolequinones; Models, Molecular; Molecular Structure; Naphthoquinones