Aziridine Carboxylates, Carboxamides and Lactones: New Methods for Their Preparation and Their Transformation into α- and β-Amino Acid Derivatives

Abstract: The preparation of a variety of novel aziridine-γ-lactones (3) from carbohydrates is described. In contrast to aziridine-2-carboxylates, the lactones react regiospecifically at C-2 with soft nucleophiles to provide optically pure substituted β-amino acid precursors. Hard nucleophiles react exclusively at the C-3 position to provide α-amino acid precursors. The utility of this methodology was demonstrated by the preparation of (3S,4S)-dihydroxy-L-glutamic acid (DHGA) from the appropriate aziridine-γ-lactone. DHGA was subsequently shown to be a selective partial agonist of mGluR1 receptors. A more concise preparation of aziridine-γ-lactones was achieved by 1,4-Michael addition of benzylamine to 2-O-triflylbutenolides. Use of a 2-O-mesylbutenolide led, under the same conditions, to the corresponding aziridine-2-carboxamides or 2-carboxylates. Finally, a new Evanstype aziridinating agent, Ses-iminoiodinane, was developed and shown to react efficiently with unsaturated substrates to give the corresponding aziridines, whose N-Ses protecting groups can be removed under mild conditions.