The chiral cyclic α,α-disubstituted α-amino acids, Hms[(–)-Men] and Hms[(+)-Men] with (–)- and (+)-menthones in their side-chains, respectively, were designed and synthesized. Hms[(–)-Men] homopeptides and Hms[(–)/(+)-Men]-containing l-Leu-based peptides were prepared in order to investigate the conformational properties of Hms[(–)/(+)-Men]. The preferred conformations of the Hms[(–)/(+)-Men]-containing peptides were determined by FTIR, ¹H NMR, and CD spectroscopy in solution, and by X-ray crystallographic analysis in the crystal state. Conformational analysis in solution revealed similar right-handed (P) 3₁₀-helical structures for the Hms[(–)/(+)-Men]-containing octapeptides. In the solid state of the hexapeptides, the peptide main-chain structures were mostly similar; however, some differences were observed in the side-chains. The Hms[(–)/(+)-Men] may function as helical inducers, but their side-chain chiralities had only a negligible effect on their helical-screw control of l-Leu-based peptides.

(R,R)-Ac₆c^4BD homopeptides form helical structures with slight control of the helical screw sense to the right-handed form. The chiral acetal moieties in (R,R)-Ac₆c^4BD are changeable in the peptide state.

Chiral bicyclic α-amino acid (R,R)-Ab_5,6=c with stereogenic centers at the γ-position of fused-ring junctions, and its enantiomer (S,S)-Ab_5,6=c, were synthesized. The CD spectra of (R,R)-Ab_5,6=c oligomers indicated that the (R,R)-Ab_5,6=c hexapeptide formed a mixture of right-handed (P)- and left-handed (M)-3₁₀-helices, while, in the (R,R)-Ab_5,6=c nonapeptide, a right-handed (P)-3₁₀-helix slightly dominated over the (M)-helix. X-Ray crystallographic analyses of (S,S)-tripeptide and (R,R)-hexapeptide revealed that both the tripeptide and hexapeptide formed a mixture of (P)- and (M)-3₁₀-helices, respectively. These results indicated that the side-chain environments around the stereogenic centers are particularly important to control the helical-screw handedness of foldamers.

Chiral cyclic α,α-disubstituted amino acids, (3S,4S)- and (3R,4R)-1-amino-3,4-(dialkoxy)cyclopentanecarboxylic acids ((S,S)- and (R,R)-Ac₅c^dOR; R: methyl, methoxymethyl), were synthesized from dimethyl L-(+)- or D-(−)-tartrate, and their homochiral homoligomers were prepared by solution-phase methods. The preferred secondary structure of the (S,S)-Ac₅c^dOMe hexapeptide was a left-handed (M) 3₁₀ helix, whereas those of the (S,S)-Ac₅c^dOMe octa- and decapeptides were left-handed (M) α helices, both in solution and in the crystal state. The octa- and decapeptides can be well dissolved in pure water and are more α helical in water than in 2,2,2-trifluoroethanol solution. The left-handed (M) helices of the (S,S)-Ac₅c^dOMe homochiral homopeptides were exclusively controlled by the side-chain chiral centers, because the cyclic amino acid (S,S)-Ac₅c^dOMe does not have an α-carbon chiral center but has side-chain γ-carbon chiral centers.