Synthesis of racemic and optically active forms of novel antimalarial agents, spirocyclopentanone–anthracene adducts, via tandem Michael addition–Dieckmann condensation reactions as the key steps

Spirocyclopentanone–anthracene adducts, novel antimalarial agents, have been synthesized by employing the racemic and the optically active dimethyl itaconate–anthracene adducts in a reaction with piperine via tandem Michael addition–Dieckmann condensation reactions as the key steps. All adducts exhibited antimalarial activity with IC50 values of 3.4–4.7 μg/mL, and importantly displayed non-cytotoxicity to vero cells.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

4′-((E)-2-(Benzo[c][1,3]dioxol-1-yl)vinyl)-3′-methoxycarbonyl-5′-(piperidine-1-carbonyl)cyclopentanone-2′-spiro-11-9,10-dihydro-9,10-ethanoanthraceneC37H35NO6Ee >99%[α]D24.4=-18.5 (c 0.87, CHCl3)Source of chirality: (−)-(1R,2S,5R)-menthol, resolutionAbsolute configuration: (3′S,4′S,5′S,11R)

4′-((E)-2-(Benzo[c][1,3]dioxol-1-yl)vinyl)-3′-methoxycarbonyl-5′-(piperidine-1-carbonyl)cyclopentanone-2′-spiro-11-9,10-dihydro-9,10-ethanoanthraceneC37H35NO6Ee >99%[α]D24.4=-70.5 (c 0.58, CHCl3)Source of chirality: (−)-(1R,2S,5R)-menthol, resolutionAbsolute configuration: (3′R,4′R,5′R,11R)