The First Fully Planar C5‐Conformation of Homooligopeptides Prepared from a Chiral α‐Ethylated α,α‐Disubstituted Amino Acid: (S)‐Butylethylglycine (=(2S)‐2‐Amino‐2‐ethylhexanoic Acid)

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.