X-Ray structures and ab initio study of the conformational properties of novel oxazole and thiazole containing di- and tripeptide mimetics

Abstract

X-Ray crystal structures of Boc-protected derivatives of the novel di- and tripeptide mimetics 2-aminomethyl-1,3-oxazole-4-carboxylic acid, 2-aminomethyl-1,3-thiazole-4-carboxylic acid, 2-(2′-aminomethyl-1′,3′-oxazol-4′-yl)-1,3-thiazole-4-carboxylic acid (gly(OxaThz)), and 2-(2′-aminomethyl-1,3-thiazol-4′-yl)-1,3-thiazole-4-carboxylic acid (gly(ThzThz)) have been determined. Furthermore conformational properties of the bicyclic compounds have been investigated by ab initio calculations at the HF and DFT level. According to the calculations for the bicyclic compounds the anti conformation is energetically more stable by about 20 kJ mol⁻¹ (HF/6-31G(d)) for gly(ThzThz) and gly(OxaThz) while in the case of gly(ThzOxa) the difference is only about 4 kJ mol⁻¹. The rotational barrier is about 28 kJ mol⁻¹ for the anti→syn conversion. Calculations at the DFT level with a 3-21G(d) basis set yielded similar results.