Design and synthesis of foldamer, and its application to asymmetric reactions

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Two kinds of optically active cyclic α,α-disubstituted α-amino acids were designed. One is a disubstituted amino acid having a cyclopentane ring (A_<C_5C>^<dOM>), and the other is a disubstituted amino acid having a piperidine skeleton (Pip). Both cyclic disubstituted amino acids have similar characteristics in that the α-carbon atom is not an asymmetric center but chiral centers exist on the cyclic side chain of the amino acids. The A_<C_5C>^<dOM> was synthesized starting from dimethyl L-tartrate as a chiral source, and the Pips were synthesized starting from dimethyl malonate and chiral amines.As a peptide-foldamer, homo- and hetero-peptides containing A_<C_5C>^<dOM> and Pip were prepared by the solution phase method The secondary structures of oligopeptides were studied in solution (in water and TFE solution) and in the solid state. It has become clear that the (S,S)-A_<C_5C>^<dOM> homopeptides having side-chain chiral centers, which do not have an asymmetric center at the α-position, form left-handed 3_<10-> and α-helices both in solution and in the solid state. It should be noted that usually short oligopeptides prepared from normal L-amino acids do not form a stable secondary structure, but short oligopeptides prepared from A_<C_5C>^<dOM> and Pip form one-handed helices. Thus, these results might be valuable for the development of asymmetric reactions using foldamers.