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)