New optically active 2H-azirin-3-amines as synthons for enantiomerically pure 2,2-disubstituted glycines

The synthesis of novel 2,2-disubstituted 2H-azirin-3-amines with a chiral a mino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers (1'R,2R)-4a-e and (1'R,2S)-4a-e ( Scheme 1. Table 1), which are synthons for the (R)- and (S)-isomers of isov aline, 2methylvaline. 2-cyclopentylalanine, 2-methylleucine. and 2-(methyl) phenylalanine, respectively. The configuration at C(2) of the synthons was determined by X-ray crystallography relative to the known configuration of the chiral auxiliary group. The reaction of 4 with thiobenzoic acid. benzoi c acid, and the dipeptide Z-Leu-Aib-OH (12) yielded the monothiodiamides 10 , the diamides 11 (Scheme 2, Table 3). and the tripeptides 13 (Scheme 3. Ta ble 4), respectively.