Molecular simplification in bioactive molecules: formal synthesis of (+)-muconin

The Journal of Organic Chemistry
Fernando R Pinacho CrisóstomoVíctor S Martín

Abstract

The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.

References

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Citations

Jun 19, 2007·Investigational New Drugs·Giovanni PetrilloMaurizio Viale
Mar 23, 2007·Bioorganic & Medicinal Chemistry Letters·Leticia G LeónJosé M Padrón
Feb 26, 2013·Angewandte Chemie·Julio Rodríguez-LópezTomás Martín
May 29, 2010·Organic & Biomolecular Chemistry·Fiona I McGonagleAndrew Sutherland
Mar 3, 2011·Organic & Biomolecular Chemistry·Sajjad AhmadAndrew Sutherland
Jun 24, 2020·Angewandte Chemie·Julio Rodríguez-LópezTomás Martín
Oct 13, 2020·European Journal of Medicinal Chemistry·Zhang-Xu HeWen Zhao
Mar 6, 2021·The Journal of Organic Chemistry·Makoto SugimotoHidefumi Makabe
May 22, 2020·Chemico-biological Interactions·Artur Christian Garcia da SilvaMarize Campos Valadares
Sep 4, 2008·Organic Letters·Shunya TakahashiHiroyuki Koshino
Sep 14, 2021·Journal of Biomolecular Structure & Dynamics·Glaucio Monteiro FerreiraAntti Poso

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