Conformation of cyclic dipeptides from empirical energy calculations

Empirical energy calculations on cyclo‐Gly‐X with X‐ Phe, Tyr, Val, and Leu as a function of the side‐chain torsion angles χ indicate that the conformation of minimum energy are characterized by χ1 = 60°, χ2 = 90° for Phe and Try, χ1 = −60° for Val and χ1 = −60°, χ2 = 180° and χ1 = 60° and χ2 = 150° for Leu. The minimum energy conformation of cyclo‐Gly‐Phe and cyclo‐Gly‐Val have the side chains of Phe and Val stacked over the poperazinedione ring as suggested by NMR and found for cyclo‐Gly‐Tyr crystal structure. In contrast, the Leu side chain is expected to exist in an extended or a quasi‐folded form.