Development of a convenient new synthetic route to [3]ferrocenophanones

Abstract

[3]Ferrocenophanone rac-8 was prepared by several non-Friedel-Crafts pathways starting from a Mannich-type coupling of 1,1'-diacetylferrocene followed by catalytic hydrogenation. Hydride abstraction from the resulting alpha-dimethylamino[3]ferrocenophane rac-14 with B(C6F5)3 followed by hydrolysis gave the ketone rac-8. Several variants of the Sommelet reaction, using ethylglyoxylate, formaldehyde or hexamethylenetetramine (urotropine) as the "oxidizing" reagent gave the alpha-[3]ferrocenophanone 8 in good to excellent yield. Some variants of these reactions were also used for the preparation of the pure enantiomer (R)-8. The electrochemical behaviour of 8 has been investigated and compared with related derivatives.

Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells

“…Selected bond distances () and bond angles (8): cisplatin ( Table 4). The correlation between the full-panel results for the two compounds was 78 % for GI 50 , 58 % for TGI, and 58 % for LC 50 values.…”

“…Comparing the mean GI 50 for each histological subpanel gives an indication of tumor selectivity, and a compound is considered selective for a tumor type if the mean GI 50 value is below the MG-MID for all cell lines (here 0.18 mm for 6 a and 0.52 mm for 6 b). Table 5 shows the mean values over each subpanel for two different experiments.…”

“…The three endpoints for each seed molecule were compared with the same endpoint for the database molecules (GI 50 , TGI, and LC 50 ). The molecule with the best correlation [Pearson correlation coefficient (PCC)] and the values for tamoxifen and cisplatin are given in Table 6.…”

“…The cells were treated for 48 h at five concentrations ranging from 0.01 to 100 mm. Three endpoints were calculated: GI 50 (the concentration where the compound inhibits cell growth by 50 %), TGI (the concentration at which the compound inhibits cell growth by 100 %), and LC 50 (the concentration at which the drug decreases the original cell number by 50 %), shown in Figure 2, as well as the MG-MID (full-panel mean-graph midpoint). Compounds 6 a and 6 b have a broad spectrum of activity, with MG-MID values (representing the average of the MG-MIDs for two experiments, using almost identical panels) lower than those for Figure 1.…”

“…[43] We have shown that the reversible ferrocene/ferricenium redox couple can catalyze the intramolecular formation of quinones when the ferrocenyl and phenol groups are linked by a conjugated system. [44] This mechanism is not limited to phenolic compounds: ferrocenyl moieties conjugated to an aniline or acetanilide group also show high activity against cancer cells, with IC 50 values of the order of 10 À7 m. [45] The structural requirements for activity seem to be 1) the presence of a ferrocene group, 2) a conjugated linker, 3) aromatic para substitution by a protic function, and 4) an ethyl group residing on the same carbon as the ferrocene group.…”