Ten-membered cyclotripeptides

Abstract

The 10-membered cyclotripeptide cyclo(-βAla-Phe-Pro-) (III) has been synthesized by cyclizing under mild conditions the linear precursor βAla-Phe-Pro-Onp·TFA. Crystal and molecular structure of (III) is reported and compared with that of the related models cyclo-(-MeAnt-Phe-Pro-) (I) and cyclo(-Hyb-Phe-Pro-) (II). Crystals of (III) are orthorhombic, C2221, with a= 8.224(1), b= 14.056(2), c= 28.559(3)A and Z = 8. The backbone of (III) is characterized by a cis-cis-trans conformation. Both the βAla-Phe and Phe-Pro peptide bonds are cis with ω values of – 14.4° and –0.1°, whereas the Pro-βAla junction exhibits trans conformation with high deviation from planarity (ω= 158.6°). The pyrrolidine ring has C2-Cβ-endo-Cγ-exo conformation and the benzylic side chain is extended toward the Phe-CO group. The molecular conformation of (III) shows a striking resemblance to that of the heterodetic model (II) and strongly differs from the all-cis conformation shown by the homodetic analogue (I).