Chiral five-membered carbocyclic ring amino acids bearing various diol acetal moieties were synthesized starting from l-malic acid, and homo-chiral homopeptides composed of cyclic amino acid (S)-Ac5 c(3EG) bearing an ethylene glycol acetal, up to an octapeptide, were prepared. A conformational analysis revealed that (S)-Ac5 c(3EG) homopeptides formed helical structures. (S)-Ac5 c(3EG) homopeptides, up to hexapeptides, formed helical structures without controlling the helical screw direction, while (S)-Ac5 c(3EG) hepta- and octapeptides formed helical structures with a preference for the left-handed (M) helical-screw direction. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 555-562, 2016.

A chiral three-membered ring C α,α -disubstituted α-amino acid (R,R)-Ac 3 c dMOM , in which the α-carbon is not a chiral center, but two side chain β-carbons are chiral centers, was synthesized from dimethyl L-(+)-tartrate, and its homopeptides were prepared. X-ray crystallographic analysis of (R,R)-Ac 3 c dMOM pentapeptide showed bent left-handed (M) 3 10 -helical structures with an unusual intramolecular hydrogen bond of the N−H•••O (ethereal) type. The lefthandedness of the bent helices was exclusively controlled by the side-chain β-carbon chiral centers.

L-Leu-based heteropeptides having (R)-or (S)-chiral five-membered carbocyclic ring amino acids (Ac 5 c 3EG ) with an ethylene acetal moiety were prepared. A conformational analysis using FT-IR absorption, 1 H NMR, and CD spectra revealed that L-Leu-based hexapeptides and nonapeptides having (R)-or (S)-Ac 5 c 3EG formed right-handed (P) helical structures in solution. An X-ray crystallographic analysis of nonapeptides 5a and 5b showed similar right-handed (P) α-helical structures, without an intramolecular hydrogen bond of the peptide N-H···-O-(acetal) type.