The First Fully Planar <i>C</i> ₅ ‐Conformation of Homooligopeptides Prepared from a Chiral <i>α</i> ‐Ethylated <i>α</i> , <i>α</i> ‐Disubstituted Amino Acid: ( <i>S</i> )‐Butylethylglycine (=(2 <i>S</i> )‐2‐Amino‐2‐ethylhexanoic Acid)

Abstract

An optically active α-ethylated α,α-disubstituted amino acid, (S)-butylethylglycine (=(2S)-2-amino-2-ethylhexanoic acid; (S)-Beg; (S)-2), was prepared starting from butyl ethyl ketone (1) by the Strecker method and enzymatic kinetic resolution of the racemic amino acid. Homooligopeptides containing (S)-Beg (up to hexapeptide) were synthesized by conventional solution methods. An ethyl ester was used for the protection at the C-terminus, and a trifluoroacetyl group was used for the N-terminus of the peptides. The structures of tri- and tetrapeptides 5 and 6 in the solid state were solved by X-ray crystallographic analysis, and were shown to have a bent planar C5-conformation (tripeptide) and a fully planar C5-conformation (tetrapeptide) (see Figs. 1 and 2, resp.). The IR and 1H-NMR spectra of hexapeptide 8 revealed that the dominant conformation in CDCl3 solution was also a fully planar C5-conformation. These results show for the first time that the preferred conformation of homopeptides containing a chiral α-ethylated α,α-disubstituted amino acid is a planar C5-conformation.