Crystal-state structures of Boc-Pro-Leu-Gly-NH2, hemihydrate and two lactam-restricted analogues

Abstract

A crystal-state structural analysis of Boc-Pro-Leu-Gly-NH₂(2a) hemihydrate and two conformationally restricted analogues that incorporate a γ- or δ-lactam modification at the –Leu-Gly– sequence, (3) and (4) respectively, has been performed by X-ray diffraction. In all three compounds the conformation of the tertiary amide group of the N^α-protecting urethane moiety is cis and the prolyl residue is semi-extended. The basic conformational feature of the published structure of H-Pro-Leu-Gly-NH₂(1), the ten-membered ring type-II β-bend structure at the C-terminus, is preserved in the N^α-t-butyloxycarbonyl derivative (2a). However, the γ- and δ-lactam modifications induce drastic changes in the backbone torsion angles of the –Leu-Gly– sequence, eventually promoting the onset of extended conformations.