A STEREOSELECTIVE SYNTHESIS OF THE (2R,3S)-3-AMINO-2-HYDROXYBUTYRIC AND (2S,3R)-3-AMINO-2-HYDROXYBUTYRIC ACID-DERIVATIVES, THE KEY COMPONENTS OF A RENIN INHIBITOR AND BESTATIN

The title synthesis was achieved by featuring the [2+2]-cycloaddition reaction of benzyloxyketene with a chiral imine derived from methyl (R)- or (S)-mandelate, alcoholysis of the formed 3,4-cis disubstituted beta-lactam under acidic conditions, and reductive removal of the mandelate-derived benzylic oxygen by way of a 2-oxazolidone derivative. Some preliminary results obtained by the [2+2]-cycloaddition reaction employing achiral and chiral imines derived from benzylamine, p-anisidine, di-panisylmethylamine, and (S)-l-phenylethylamine were also reported. Stereoselectivity of the [2+2]-cycloaddition reaction could be explained by the initial formation of a zwitter-ionic intermediate and its subsequent conrotatory ring closure.