APPLICATIONS OF THE MITSUNOBU REACTION IN PEPTIDE CHEMISTRY

The 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 ac tive compounds. The paper deals with applications of the Mitsunobu rea ction in amino acid and peptide chemistry. The process provides easy a ccess to many unnatural amino acids and derivatives. Since the reactio n 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 beta-hydroxy amino acid cont aining peptides under Mitsunobu reaction conditions leads to a constra ined peptide that mimics the stabilizing reverse turn secondary struct ure. (C) 1998 European Peptide Society and John Wiley & Sons, Ltd.