Description:
<jats:title>Abstract</jats:title><jats:p>The dipeptide isostere 5‐aminothiophene carboxylic acid has been combined with <jats:sc>L</jats:sc>‐phenylalanine moieties to provide linear and cyclic hybrid oligopeptides. A suitable protecting group strategy and appropriate coupling methods have been developed to guarantee a high degree of enantiopurity of the resulting amides. Cyclic tetraamides have been efficiently obtained by macrocyclization of the linear derivatives. In the case of racemized cyclization precursors, two diastereomeric macrocycles (<jats:italic>S</jats:italic>,<jats:italic>S</jats:italic>/<jats:italic>R</jats:italic>,<jats:italic>R</jats:italic> and <jats:italic>meso</jats:italic>) have been isolated. Their crystal structures show clear effects of the stereogenic centers on the ring conformations and molecular packing.</jats:p>