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

An optically active α ‐ethylated α , α ‐disubstituted amino acid, ( S )‐butylethylglycine (=(2 S )‐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 C 5 ‐conformation (tripeptide) and a fully planar C 5 ‐conformation (tetrapeptide) (see Figs. 1 and 2 , resp.). The IR and 1 H‐NMR spectra of hexapeptide 8 revealed that the dominant conformation in CDCl 3 solution was also a fully planar C 5 ‐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 C 5 ‐conformation.