The first oxalamide‐bridged ferrocene: Facile synthesis, preliminary conformational analysis and biological evaluation

Abstract

tert‐Butyl‐1′‐methoxycarbonyl‐1‐ferrocenecarbamate (1) was Boc‐deprotected to give free amine which underwent oxalyl chloride‐mediated dimerization. The structure of the so‐obtained oxalamide‐bridged ferrocene 2 was elucidated using infrared and NMR (1H, 13C, COSY, NOESY, HSQC, HMBC) spectroscopies, crystal structure analysis, and electrospray ionization and high‐resolution mass spectrometry. The preliminary conformational analysis in solution suggested the intramolecular engagement of oxalamide protons, while single‐crystal analysis revealed an intermolecular hydrogen‐bonding pattern. Also, the effect of oxalamide‐bridged ferrocene 2 on cell viability of three human cell lines (HEK293T, HeLa and HepG2) was tested. In vitro screening revealed proliferative as well as cytotoxic effects of the tested compound in the applied concentration range (1–350 μM) on HEK293T and HepG2 cells. Stimulatory effect on cell growth was the most pronounced for normal HEK293T cells, while the highest cytotoxic effect was observed towards HeLa tumour cells and it was dose‐dependent. The observed dual biological activity of 2 implies its potential application in drug development.

Oxalamide-Bridged Ferrocenes: Conformational and Gelation Properties and In Vitro Antitumor Activity

“… a Adapted from ref : N.D.= not detected and N.T.= not tested in ref . b Adapted from ref . c Adapted from ref . …”

“…(a) Bis­(amino acid) ( I ) and bis­(amino alcohol) oxalamide gelators ( II ), (b) ferrocene oxalamide ( III ), and (c) novel ferrocene oxalamides 3 and 4 .…”

“…With these studies in mind, we had synthesized compound III containing two ferrocene units connected by an oxalamide bridge (Figure b) . Spectroscopic analysis in nonpolar CH 2 Cl 2 or CDCl 3 suggested the conformational pattern based on NH···OC COOMe intramolecular hydrogen bonds (IHBs).…”

Ferrocene Bioconjugates

“…[64][65][66] With this in mind, we have synthesized oxalamidebridged ferrocene 17 (Scheme 3), and have tested its cytotoxic and gelation potential. [67] Boc-deprotection of compound 16 in the presence of gaseous HCl, followed by treatment of the hydrochloride salt with NEt3 gave free amine. The addition of oxalyl-chloride enabled the bridging of the two ferrocene moieties by oxalamide unit.…”

Application of the Curtius rearrangement to the synthesis of 1′-aminoferrocene-1-carboxylic acid derivatives

“…[15][16][17][18] It has also been used to access polyferrocenic structures to study electronic communication between the redox-active units [19][20][21][22][23][24][25][26] and in various scaffolds for specific applications. [27][28][29][30][31][32][33][34][35][36] Surprisingly, despite the wide use of Fca, the price of its commercially available N-protected derivatives remains expensive, probably due to the lack of easy and fast syntheses. The first approach was reported by Butler and co-workers in 1998 starting from 1,1'-dibromoferrocene (Scheme 1, A).…”