Study of the conformational profile of the cyclohexane analogs of L-phenylalanine.

Abstract

The conformational profile of the conformationally constrained cyclohexane analogs of phenylalanine (1-amino-2-phenylcyclohexanecarboxylic acids, c6Phe) was assessed using computational methods. For this purpose, the conformational space of the N-acetyl methylamide derivatives of the stereoisomers (2S,3R)c6Phe and (2S,3S)c6Phe was explored by computing their respective Ramachandran maps, and low-energy minima were characterized at molecular mechanics level by means of the AMBER program, using the parm94 force field set of parameters. In order to assess the performance of the molecular mechanics calculations, each of the low-energy conformations was also investigated further at the ab initio level. Accordingly, the molecular mechanics geometries were used as starting conformations to perform full geometry optimizations at the Hartree-Fock level, using a 6-31G(d) basis set. Analysis of the results revealed that the cyclohexane structure directly induces some restrictions on the backbone, and constrains the orientation of the aromatic side-chain to two narrow regions for each stereoisomer. The conformational profile of these amino acids is then explained on the grounds of the interaction between the rigidly held phenyl ring and the main chain NH and CO groups. The results obtained are in good accordance with the experimental observations.