AbstractThe Mitsunobu reaction – the nucleophilic substitution of an alcoholic hydroxyl group mediated by the redox system trialkylphosphine/dialkyl azodicarobxylate – is widely used in the chemistry of biologically active compounds. The paper deals with applications of the Mitsunobu reaction in amino acid and peptide chemistry. The process provides easy access to many unnatural amino acids and derivatives. Since the reaction occurs with complete inversion of the configuration at the carbinol chiral centre, it can be used for the synthesis of diastereoisomers of hydroxy‒ and tioprolines. Cyclization of β‒hydroxy amino acid containing peptides under Mitsunobu reaction conditions leads to a constrained peptide that mimics the stabilizing reverse turn secondary structure. © 1998 European Peptide Society and John Wiley&