Cyclodepsitripeptides. Synthesis, crystal structures and molecular conformations of cyclo(-L-2-hydroxyisovaleryl-L-prolyl-L-prolyl-) and cyclo(-D-2-hydroxyisovaleryl-L-prolyl-L-prolyl-)

Abstract

The molecular and crystal structures of two diastereoisomeric nine-membered-ring heterodetic cyclotripeptides have been studied by X-ray analysis and compared with those of homodetic ring systems. cyclo(-Hylv-Pro-Pro-)(LLL) and cyclo(-D-Hylv-Pro-Pro-)(DLL) have been synthesized, through lactone-bond formation, starting from the corresponding linear precursors. The prolyl residues possess approximate C₂ symmetry in LLL and C_S symmetry in DLL. All peptide bonds adopt the cis-conformation and the two lactone bonds the trans-conformation. The most pronounced deviation from planarity is shown by the Pro-Pro bond in LLL (ω₂=+22.6°) and by the lactone bond in DLL (ω₃=–153.6°). An unusual value of the (θ–φ) parameter (36.8°) was found for Pro₃ in LLL; this has been related to the pyramidality of N₃. The C₂ pseudosymmetry assigned to the backbone conformations of LLL and DLL is discussed and compared with that of cyclo(-Pro₂-D-Pro-).