An ab Initio Study of Intramolecular Hydrogen Bondings in α-Hydroxy Ketomethylene Dipeptide Isostere

Ab initio calculations of the representative α-hydroxy ketomethylene dipeptide isostere (2S,5S)-5-amino-2-hydroxy-4-oxohexanoic acid (1) are described. All calculations including full geometry optimizations were performed at the MP2/6-31G* level. In the gas phase, 12 low-energy conformers are located by minimizing geometries assembled from stable molecular fragments. Among these conformers, six structurally similar conformers, in which the 2-hydroxyl group forms hydrogen bondings with both the O atom of the 4-carbonyl group in 1,3-fashion and the O atom of 1-carboxylic acid in 1,2-fashion simultaneously, are found to be particularly stable. Thus, the conformational preference of 1 appears to be governed by arrangements and strength of intramolecular hydrogen bondings. To examine conformational natures of 1 in solutions more accurately, we corrected the thermochemical properties and carried out self-consistent reaction field calculations. Going from the gas phase to solutions, the basic features of the conformational preferences in 1 also appear to be maintained in solutions including a highly polar aqueous medium, despite slight changes in the population of each conformer.