Cyclols, cyclodepsipeptides, and N-acyl-diketopiperazines from linear precursors. Synthesis and crystal structure of 10-membered cyclodepsipeptides.

Abstract

In order to investigate the relative formation tendency of different tautomeric ring systems (cyclols, cyclodepsipeptides and corresponding N-acyl-diketopiperazines), two linear peptide precursors containing proline as C-terminal residue, have been synthesized and subjected to cyclizing conditions. Boc-Ser-Phe-Pro-ONp (I) gave three isomeric cyclic compounds: Boc-Ser-Phe-Pro- (IV), N-(Boc-Ser)-cyclo-(Phe-D-Pro) (III) and the corresponding aza-cyclol (II). Starting from Hyb-Phe-Pro-ONp (V) two epimeric N(3-hydroxybutyryl)diketopiperazines (VI) and (VII) and the corresponding 10-membered cyclodepsipeptide (VIII) could be isolated. Crystal and molecular structure of VIII is reported. Crystals of VIII are orthorhombic, P212121 with a = 9.684, b = 22.985, c = 7.841, z = 4. The two peptidic bonds are cis with omega values of 6.6 degrees and - 18.1 degrees, whereas the lactonic bond is of transoid type. The pyrrolidine ring has C2-C gamma-exo conformation.