Conformational Analysis of Heteroannularly Substituted Ferrocene Oligoamides

Abstract

The main conformer of symmetrical conjugates of ferrocene‐1,1′‐dicarboxylic acid with natural amino acids – Fn(CO–AA1–2–OMe)2 (type I, Fn = ferrocene‐1,1′‐diyl, AA = L‐α‐amino acid) – is supported by two hydrogen bonds between the peptide substituents. To compare intramolecular hydrogen bond patterns of type I conjugates with related asymmetrically substituted derivatives, type II (MeNHCO–Fn–CO–AA–OMe) and type III conjugates (MeNHCO–Fn–CO–AA–NHMe) were prepared in moderate‐to‐good yields in a few steps starting from 1′‐(methoxycarbonyl)ferrocene‐1‐carboxylic acid by using the HOBt/EDC method (AA = Gly, Ala, Val). 1H NMR spectroscopic variation ratio analysis suggests that an increase in the steric demand of the amino acid side chains favours conformations with hydrogen‐bonded FnCONHMe groups. CD spectroscopy of chiral derivatives reveals that (P)‐helical conformations predominate in solution. The experimental findings are in accordance with DFT calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Preparation and Conformation Analysis of N‐(Ferrocenoyl)dipeptide Esters and Their 1′‐Acetyl Derivatives

“…For this paper we have performed complete conformation space searches for compounds 3-6 in chloroform solution. The number of NH groups was smaller than in the previously described type III substrates (Scheme 1), [21] thus making the analysis less computationally demanding.…”

C2‐Symmetric Ferrocene–Bis(ureido)peptides: Synthesis, Conformation and Solid‐State Structure

“…This combination of methods has been previously successfully applied for analysing bioconjugates of ferrocene derivatives. [19,23,[25][26][27]31,33,36,38] The hydrogen-acceptor site of hydrogen bonds is easily seen by IR spectroscopy. The IR data of 3 indicate hydrogen bonds to the ester carbonyl CO ester , whereas in 4 hydrogen bonds to the amide carbonyl CO amide are observed ( Table 1).…”

“…[19,23,[25][26][27]31,33,36,38] To gain some further insight, DFT calculations (B3LYP/LanL2DZ [52] ) and optimisations were performed on full complexes 3 and 4 without any symmetry constraints (Figures 7 and 8). In fact, highly unsymmetrical starting geometries converged to almost C 2 -symmetric optimised conformations in both cases (bottom of Figures 7 and 8).…”

Conformational Analysis of β‐Lactam‐Containing Ferrocene Peptides

“…[44b, 61] The 1 H NMR spectra of 8 and 12-14 suggest that the proton of the NH Alm group is involved in hydrogen bonds in all cases, as these protons resonate at fields well below δ = 7 ppm in CDCl 3 , and according to the previous statement the shift variations ∆δ = 0.76 (for 8), 0.60 (for 12), 0.53 (for 13), and 0.62 (for 14) ppm indicate medium strong hydrogen bonds (Table 2). Furthermore, the resonances are only weakly dependent on the concentration (Figures 2 and 3), which thus suggests participation of NH Alm in intramolecu- lar hydrogen bonds in molecules 8 and 12-14.…”