Thiazole amino acids Hantzsch synthesis

Various more or less efficient methods have been reported for the synthesis of 2-(l-ami-noalkyl)thiazole-4-carboxylic acids and their suitably protected derivatives. 237,539,541,558-568 Optimal conditions must be selected in these syntheses to prevent racemization at the chiral aminoalkyl moiety, e.g. when applying a modified Hantzsch synthesis 559 racemization has been observed to occur at the level of the starting Na-protected amino acid thioamide as well as in the base-mediated dehydration step of the intermediate hydroxydihydrothiazoles. 558 The 2-(aminoalkyl)thiazole-4-carboxylic acids are incorporated into the linear precursors by standard procedures of peptide synthesis, 237,514,529,539,552,555,558,564,569 and cyclization is pref-... 

Thiazol-a-amino acids (441) can be prepared by the Hantzsch thiazole synthesis of the thioamide... 

The Hantzsch synthesis has been used to prepare a number of natural and synthetic cyclic peptides incorporating thiazoles. Pattenden and coworkers used the Hantzsch thiazole synthesis in their preparation of an N-Boc protected L-proline thiazole based amino acid, which was subsequently used to generate cyclic hexaeptides and octapeptides. Thioamide 165, prepared from commercially available Boc-L-proline, was subjected to Holzapfel s modified conditions to generate the desired thiazole 166 in 61% yield. The biological evaluation of these compounds is currently under investigation. 

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