Dedicated to Professor Edgar Heilbronner on the occasion of his 80th birthdayThe synthesis of novel 2,2-disubstituted 2H-azirin-3-amines with a chiral amino 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 isovaline, 2-methylvaline, 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, benzoic 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, Table 4), respectively.

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The synthesis of a novel 2,2-disubstituted 2H-azirin-3-amine 10 as a building block for racemic Glu(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 10 with thiobenzoic S-acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 17 and the dipeptide 18 as a mixture of diastereoisomers, respectively (Scheme 2). From 18, each of the protecting groups was removed selectively (Scheme 3).

The synthesis of a novel 2,2-disubstituted 2H-azirin-3-amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme 2). In 11, each of the protecting groups was removed selectively (Scheme 3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1-(naphthalen-1-yl)ethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme 2). However, the diastereoisomers of the synthons 3b and 3c could not be separated by chromatography. The synthesis of a novel 2,2-disubstituted 2H-azirin-3-amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme 2). In 11, each of the protecting groups was removed selectively (Scheme 3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1-naphthylethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme 2).However, the diastereoisomers of the synthons 3b and 3c could not be separated by means of chromatography.3

The synthesis and conformational analysis of model pentapeptides with the sequence Z‐Leu‐Aib‐Xaa‐Gln‐Valol is described. These peptides contain two 2,2‐disubstituted glycines (α,α‐disubstituted α‐amino acids), i.e., Aib (aminoisobutyric acid), and a series of unsymmetrically substituted, enantiomerically pure amino acids Xaa. These disubstituted amino acids were incorporated into the model peptides via the ‘azirine/oxazolone method’. Conformational analysis was performed in solution by means of NMR techniques and, in the solid state, by X‐ray crystallography. Both methods show that the backbones of these model peptides adopt helical conformations, as expected for 2,2‐disubstitued glycine‐containing peptides.