Synthesis of anti-proliferative [3.3.0]furofuranone derivatives by lactonization and functionalization of C-glycosyl compounds.
Fiche publication
Date publication
juillet 2021
Journal
Bioorganic & medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BOURA Cédric
Tous les auteurs :
Ariztia J, Chateau A, Boura C, Didierjean C, Lamandé-Langle S, Pellegrini Moïse N
Lien Pubmed
Résumé
The [3.3.0]furofuranone structure is found in numerous families of biologically active natural products. We took advantage of the stereodiversity afforded by carbohydrate derivatives to prepare several compounds structurally similar to goniofufurone and crassalactones which are natural cytotoxic agents. We designed and synthesized several stereoisomers of these natural compounds via lactonization of C-glycosyl compounds bearing an hydroxyl on position 4 and a methyl ester on the pseudo-anomeric positionThe reactivity of this bicyclic moiety was explored through etherification of hydroxyls in position 5 and 7 and various substituants (halogen, phenyl, benzyl, cynanmoyl) were introduced. The anti-proliferative properties of these mimics were then evaluated on various cancer cell lines and two compounds 24 and 35 demonstrated IC value of 1.34 µM (U251) and 7.60 µM (U87) respectively.
Mots clés
Anti-proliferative compound, C-glycosyl compound, Furofuranone
Référence
Bioorg Med Chem. 2021 Jul 21;45:116313