Bioconjugates of 1′‐Aminoferrocene‐1‐carboxylic Acid with (<i>S</i>)‐3‐Amino‐2‐methylpropanoic Acid and <scp>L</scp>‐Alanine

Abstract

Abstract Formal CH 2 insertion in bioconjugates composed of 1′‐aminoferrocene‐1‐carboxylic acid (Fca) and alanine Boc‐Ala‐Fca‐Ala‐OCH 3 gives Fca bioconjugates with the β‐amino acid ( S )‐3‐amino‐2‐methylpropanoic acid (Aib). The novel homologous conjugates of ferrocene were fully characterized by spectroscopic and analytical methods. NMR, CD and IR spectroscopy in concert with DFT calculations suggest that the formal “ L ‐Ala–to–( S )‐β‐Aib mutations” can exert ferrocene helix inversion due to the different stereogenic carbon atoms of L ‐Ala and ( S )‐β‐Aib. Furthermore, the mutation (de‐)stabilizes the conserved secondary structure with two intramolecular hydrogen bonds, depending on the “mutation site”. The systematic work presented provides a firm basis for understanding the factors that determine folding in bioconjugates of ferrocene and β‐amino acids and will guide the rational design of metallocene peptidomimetics incorporating β‐amino acids.