Constrained analogs of methionine: asymmetric synthesis of χ-angle restricted methionine derivatives through [3.1.0]-γ-lactone cyclopropane ring opening

Abstract

Regiospecific and stereoselective ring opening of a [3.1.0]-γ-lactone intermediate by sulfur-containing nucleophiles has been developed. The reaction product was confirmed by NMR techniques and chemical equilibrium processes. Using this approach, all four possible diastereomers of χ-angle restricted methionine surrogates have been synthesized by electrophilic azidation and reduction to the amino group. These constrained analogs can be used in the preparation of peptidomimetics of sequences containing methionine in the C-terminal position.