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

The conformational profile of the conformationally constrained cyclohexane analogs of phenylalanine (1-amino-2-phenylcyclohexanecarboxylic acids, c(6) Phe) was assessed using computational methods. For this purpose, the confor mational space of the N-acetyl methylamide derivatives of the stereoisomers (2S,3R)c(6)Phe and (ZS,3S)c(6)Phe was explored by computing their respecti ve Ramachandran maps, and low-energy minima were characterized at molecular mechanics level by means of the AMBER program, using the parm94 force fiel d set of parameters. In order to assess the performance of the molecular me chanics calculations, each of the low-energy conformations was also investi gated further at the ab initio level. Accordingly, the molecular mechanics geometries were used as starting conformations to perform full geometry opt imizations at the Hartree-Fock level, using a 6-31G(d) basis set. Analysis of the results revealed that the cyclohexane structure directly induces som e restrictions on the backbone, and constrains the orientation of the aroma tic side-chain to two narrow regions for each stereoisomer, The conformatio nal profile of these amino acids is then explained on the grounds of the in teraction 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.