Oxazolopiperidin-2-ones as Type II‘ β-Turn Mimetics: Synthesis and Conformational Analysis

Abstract

We describe a straightforward synthesis of 9-substituted 3-aminooxazolidinopiperidin-2-ones 4. Some derivatives were prepared for use in peptide synthesis as rigidified surrogates of the Ala-Pro dipeptide. Analysis of the amide derivatives 14 by NMR experiments and molecular mechanics/dynamics calculations shows that the major isomer 14a has a stronger propensity than the minor isomer 14b to adopt β-turn conformations, and the calculations indicate that in water 14a adopts a stable βII‘ turn conformation.