Cyclic α,α‐Disubstituted α‐Amino Acids with Menthone in Their Side‐Chains Linked through an Acetal Moiety and Helical Structures of Their Peptides

Abstract

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.