One-Handed Helical Screw Direction of Homopeptide Foldamer Exclusively Induced by Cyclic α-Amino Acid Side-Chain Chiral Centers

Abstract

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.