Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

• Published in: Chemistry : a European journal 2017-12, Vol.23 (72), p.18120-18124
• Main Authors: Eto, Ryo, Oba, Makoto, Ueda, Atsushi, Uku, Tsubasa, Doi, Mitsunobu, Matsuo, Yosuke, Tanaka, Takashi, Demizu, Yosuke, Kurihara, Masaaki, Tanaka, Masakazu
• Format: Article
• Language: English
• Subjects: Alpha rays; Amino acids; Butane; Chemistry; chirality; conformation analysis; Crystallography; foldamers; Handedness; helical structures; Helices; Hydrogenation; Peptides; Temperature preferences
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201705306

The relationship between chiral centers and the helical‐screw control of their peptides has already been reported, but it has yet to be elucidated in detail. A chiral four‐membered ring α,α‐disubstituted α‐amino acid with a (R,R)‐butane‐2,3‐diol acetal moiety at the γ‐position, but no α‐chiral carbon, was synthesized. X‐ray crystallographic analysis unambiguously revealed that its homo‐chiral heptapeptide formed right‐handed (P) and left‐handed (M) 310‐helical structures at a ratio of 1:1. They appeared to be enantiomeric at the peptide backbone, but diastereomeric with fourteen (R)‐configuration chiral centers. Conformational analyses of homopeptides in solution also indicated that diastereomeric (P) and (M) helices existed at approximately equal amounts, with a slight preference toward right‐handedness, and they quickly interchanged at room temperature. The circumstances of chiral centers are important for the control of their helical‐screw direction. Do the twist: The relationship between the right‐handed (P) and left‐handed (M) helices of the (R,R)‐Ac4c3BD heptapeptide appears to be enantiomeric at the peptide backbone. However, these helices are diastereomeric because both helices have fourteen (R)‐configuration chiral centers.