Total synthesis and anticancer activities of (-)- and (+)-thespesone.

Abstract

The natural p-naphthoquinone (-)-thespesone 1 and its (+)-enantiomer were synthesized for the first time by bisacylation of a 5-lithiodihydrobenzofuran 2' with 4-methyl-3-tert-butoxycyclobut-3-ene-1,2-dione 3. The racemate of the required 2-arylpropan-1-ol precursor 10 was kinetically resolved by an enzyme-catalyzed acetylation exclusively of the (S)-enantiomer. Saponification of this acetate mediated by the same enzyme, porcine pancreas lipase (PPL), afforded the (S)-2-arylpropan-1-ol in 96% ee. Its unreacted (R)-enantiomer could be obtained with 77% ee. (-)-(S)-thespesone was far more efficacious against a panel of six cancer cell lines including multiresistant ones than its (+)-enantiomer and also when compared to thymoquinone, an established natural antitumoral p-quinone from Nigella sativa. Unlike the latter, (-)-thespesone was well tolerated by nonmalignant fibroblasts.

• Authors: Sandra Breyer, Katharina Effenberger-Neidnicht, Rainer Schobert
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 75 Issue 18 Pg. 6214-8 (Sep 17 2010) ISSN: 1520-6904 [Electronic] United States
• PMID: 20712304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Naphthoquinones
• thespesone

Topics

• Antineoplastic Agents (chemical synthesis, chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Molecular Structure
• Naphthoquinones (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship