The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

Abstract

A novel synthetic approach toward a poorly explored bioorganometallic consisting of ferrocene-1,1'-diamine bearing structurally and chirally diverse amino acid sequences is reported. Until now, ferrocene-1,1'-diamine was suitable for accommodating only identical amino acid sequences at its N-termini, leading to the symmetrically disubstituted homochiral products stabilized through a 14-membered intramolecular hydrogen-bonded ring as is seen in antiparallel β-sheet peptides. The key step of the novel synthetic pathway is the transformation of Ac-Ala-NH-Fn-COOH (5) (Fn = 1,1'-ferrocenylene) to orthogonally protected Ac-Ala-NH-Fn-NHBoc (7). The spectroscopic analysis (IR, NMR, CD) of the novel compounds, corroborated with DFT studies, suggests the interesting feature of the ferrocene-1,1'-diamine scaffold. The same hydrogen-bonding pattern, i.e. a 14-membered hydrogen-bonded ring, was determined both in solution and in the solid state, thus making them promising, yet simple scaffolds capable of mimicking β-sheet peptides. In vitro screening of potential anticancer activity in Hep G2 human liver carcinoma cells and Hs 578 T human breast cancer cells revealed a cytotoxic pattern for novel compounds (150-500 μM) with significantly decreased cell proliferation.

Synthesis and Conformational Study of Monosubstituted Aminoferrocene‐Based Peptides Bearing Homo‐ and Heterochiral Pro‐Ala Sequences

“…The research described in our previous papers usually includes a computational study to obtain a complete picture regarding the hydrogen bonding in ferrocene derivatives , , , , . Here, we again employed an approach in which molecular and quantum mechanics are combined to achieve a relatively fast search of the conformational space.…”

“…Ferrocene (Fc) and its derivatives have attracted wide attention in recent years owing to their specific structural properties and potential applications in bioorganometallic and bioanalytical chemistry . One group of ferrocene bioconjugates, namely, ferrocene peptides, came into focus because of their ability to mimic the secondary structures of proteins . The distance of 3.3 Å between the two cyclopentadienyl (Cp) rings promotes intramolecular hydrogen bonding between two peptide chains attached to the rings of the ferrocene unit , …”

Ferrocenyl GNA Nucleosides: A Bridge between Organic and Organometallic Xeno‐nucleic Acids

“…With the following experiments, we aimed to correlate the established stereochemistry of both enantiomers with CD spectra in solution. CD spectra are excellent for establishing and predicting the absolute configurations for ferrocene derivatives . Therefore, they can be used as guides for the assignment of the absolute configuration of new ferrocenyl nucleobases if X‐ray crystal structures are not available.…”

Synthesis, spectral characterization and inhibitory potency of ferrocene‐containing mannosides towards type 1 fimbriated Escherichia coli

“…Also, the acids 3 and 4 underwent the 'azide' procedure for carbamate synthesis. [23,[30][31][32][33] The unstable azides 7 and 8, obtained by action of Et 3 N and ClCOOEt, were subjected in situ to the Curtius rearrangement by heating with freshly dried t-BuOH to give carbamates 9 and 10. In order to prevent the undesired conversion of the intermediate isocyanate group to the corresponding urea, the rearrangement temperature was limited to 65°C.…”