title: Atypical McMurry cross-coupling reactions leading to a new series of potent antiproliferative compounds bearing the key [ferrocenyl-ene-phenol] motif.
abstract: In the course of the preparation of a series of ferrocenyl derivatives of diethylstilbestrol (DES), in which one of the 4-hydroxyphenyl moieties was replaced by a ferrocenyl group, the McMurry reaction of chloropropionylferrocene with a number of mono-aryl ketones unexpectedly yielded the hydroxylated ferrocenyl DES derivatives, 5a-c, in poor yields (10%-16%). These compounds showed high activity on the hormone-independent breast cancer cell line MDA-MB-231 with IC50 values ranging from 0.14 to 0.36 µM. Surprisingly, non-hydroxylated ferrocenyl DES, 4, showed only an IC50 value of 1.14 µM, illustrating the importance of the hydroxyethyl function in this promising new series. For comparison, McMurry reactions of the shorter chain analogue chloroacetylferrocene were carried out to see the difference in behaviour with mono-aryl ketones versus a diaryl ketone. The effect of changing the length of the alkyl chain adjacent to the phenolic substituent of the hydroxylated ferrocenyl DES was studied, a mechanistic rationale to account for the unexpected products is proposed, and the antiproliferative activities of all of these compounds on MDA-MB-231 cells lines were measured and compared. X-ray crystal structures of cross-coupled products and of pinacol-pinacolone rearrangements are reported.
authors.affiliation: Chimie ParisTech, 11 rue Pierre et Marie Curie, Paris F75231 Paris cedex 05, France. pascal.pigeon@chimie-paristech.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigeon
authors.affiliation: Chimie ParisTech, 11 rue Pierre et Marie Curie, Paris F75231 Paris cedex 05, France. meralgormen@gmail.com.
authors.forename: Meral
authors.initials: M
authors.lastname: Görmen
authors.affiliation: Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland. konkow@chemia.uni.lodz.pl.
authors.forename: Konrad
authors.initials: K
authors.lastname: Kowalski
authors.affiliation: UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland. helge.muellerbunz@ucd.ie.
authors.forename: Helge
authors.initials: H
authors.lastname: Müller-Bunz
authors.affiliation: UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland. michael.mcglinchey@ucd.ie.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McGlinchey
authors.affiliation: Sorbonne Universités, UPMC univ Paris 6, Institut Parisien de Chimie Moléculaire (IPCM) - UMR 8232, 4 place Jussieu, 75252 Paris Cedex 05, France. siden.top@upmc.fr.
authors.forename: Siden
authors.initials: S
authors.lastname: Top
authors.affiliation: Chimie ParisTech, 11 rue Pierre et Marie Curie, Paris F75231 Paris cedex 05, France. gerard.jaouen@upmc.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Jaouen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D000075163:Metallocenes; D015394:Molecular Structure; D019800:Phenol / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D019800:Phenol; C004998:ferrocene