Book of Abstracts - Ruhr-Universität Bochum

OP-13
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Ferrocenyl Flavonoids: Synthesis and Antiproliferative Effects
Elizabeth A. Hillard, a Jean-Philippe Monserrat, a Guy Chabot, b Louis Hamon, c and Gérard Jaouen c
a Chimie ParisTech (Ecole Nationale Supérieure de Chimie de Paris), Laboratoire Charles Friedel,
UMR CNRS 7223, 11 rue Pierre et Marie Curie, 75231 Paris cedex 05, France. b Chimie ParisTech
(Ecole Nationale Supérieure de Chimie de Paris), Département Friedel; Université Paris Descartes,
Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacologie Chimique,
Génétique et Imagerie (CNRS UMR 8151- INSERM U 1022), 4 avenue de l’Observatoire, 75006
Paris, France. c Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, Université Pierre et Marie
Curie, CC47, 4 Place Jussieu, 75252 Paris Cedex 05, France.
Flavonoids, such as flavanones and flavones, are ubiquitous plant-based polyphenols. Their
importance in health was first reported in 1936, 1 and numerous benefits have been reported for various
conditions including cancer, cardio-vascular diseases, asthma, and viral infections Several pathways
for chemoprevention have been elucidated, particularly protective antioxidant properties. However,
some flavonoids, such as quercetin, are also known to act as prooxidants because they can be
metabolized to o-quinones and quinone methides that subsequently produce ROS, which have been
proposed as a way to stimulate apoptosis in cancer cells. 2 Because of the dual antioxidant/prooxidant
actions of flavonoids, we therefore became interested in modifying these compounds with redoxactive
ferrocene and screening them against cancer cells.
O
chalcone
O
O
aurone
O
O
flavone
O
O
flavanone
29
HO
O
O
OH
OH O
quercetin
Fe
OH
ferrocenyl chalcone
It is remarkable, that, although ferrocenyl chalcones have been widely studied for over 50 years, 3 there
is, to our knowledge, no report of the corresponding ferrocenyl flavones or flavanones. We have
recently discovered a novel reaction which gives easy access to the first ferrocenyl flavones, via a
ferricenium intermediate. 4 The ferrocenyl flavones, furthermore, isomerize under basic conditions to
give access to a class of ferrocenyl aurones. We have also been able to graft ferrocene to the flavanone
skeleton via an acid-catalyzed condensation reaction. The synthesis of these new compounds and
preliminary in vitro antiproliferative results will be presented.
References
1. S. Rusznyak, A. Szent-Gyorgyi, Nature 1936, 138, 27.
2. H. Pelicano, D. Carney, P. Huang, Drug Resist. Update 2004, 7, 97-110.
3. C. R. Hauser, J. K. Lindsay, J. Org. Chem. 1957, 22, 482-485.
4. J-P Monserrat, G. G. Chabot, L. Hamon, L. Quentin, D. Scherman, G. Jaouen, E. A. Hillard, Chem.
Commun., 2010, in press.
OH