New Optically Active 2H-Azirin-3-amines as Synthons for Enantiomerically Pure 2,2-Disubstituted Glycines: Synthesis of Synthons for Tyr(2Me) and Dopa(2Me), and Their Incorporation into Dipeptides

Abstract

The synthesis of novel unsymmetrically 2,2-disubstituted 2H-azirin-3-amines with chiral auxiliary amino groups is described. Chromatographic separation of the mixture of diastereoisomers yielded (1′R,2S)-2a,b and (1′R,2R)-2a,b (c.f. Scheme 1 and Table 1), which are synthons for (S)- and (R)-2-methyltyrosine and 2-methyl-3′,4′-dihydroxyphenylalanine. Another new synthon 2c, i.e., a synthon for 2-(azidomethyl)alanine, was prepared but could not be separated into its pure diastereoisomers. The reaction of 2 with thiobenzoic acid, benzoic acid, and the amino acid Fmoc-Val-OH yielded the monothiodiamides 11, the diamides 12 (cf. Scheme 3 and Table 3), and the dipeptides 13 (cf. Scheme 4 and Table 4), respectively. From 13, each protecting group was removed selectively under standard conditions (cf. Schemes 5–7 and Tables 5–6). The configuration at C(2) of the amino acid derivatives (1R,1′R)-11a, (1R,1′R)-11b, (1S,1′R)-12b, and (1R,1′R)-12b was determined by X-ray crystallography relative to the known configuration of the chiral auxiliary group.