Synthesis of Chiral Cyclic α,α-Disubstituted α-Amino Acid Having a Property of a Right-handed α-Helix Formation, and Its Function

Abstract

We have developed a practical synthetic route of optically active cyclic α,α-disubstituted α-amino acids; (3S,4S)- and (3R,4R)-1-amino-3,4-di(methoxy)cyclopentanecarboxylic acids (Ac5cdiOM) starting from dimethyl L-(+)- and D-(-)-tartrate, respectively. These amino acids (S,S)- and (3R,4R)-Ac5cdiOM were introduced into L-leucine sequences by the solution-phase methods using EDC as a coupling reagent, and the conformations of their heteropeptides have been studied by using X-ray crystallographic analysis, FT-IR, and CD spectra. It has become clear that the propensity of cyclic α,α-disubstituted α-amino acid (3R,4R)-Ac5cdiOM is to form a right-handed (P) alpha-helix, whereas that of Aib is to form both right-handed (P) and left-handed (M) 310-helices.

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