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 (19R,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.