Interplay of Pyrrolidine Units with Homo/Hetero Chirality and CF3–Aryl Substituents on Secondary Structures of β‑Proline Tripeptides in Solution

All possible variants of β-proline functionalized tripeptides consisting of homo/hetero chiral monomeric all-cis 5-arylpyrrolidine-2,4-dicarboxylate units were synthesized for the first time by a nonpeptidic coupling method based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Secondary structures of β-proline tripeptides in solution were determined using the NMR spectroscopy data. o-(Trifluoromethyl)­phenyl substituent contributes to stereoselectivity of 1,3-dipolar cycloaddition and structural features of β-proline tripeptides. A β-proline CF3-tripeptide with alternating absolute chirality between adjacent pyrrolidine units mimics natural PPII helix secondary structure.