S. Cerrini

Peptidic cyclols. Synthesis, and crystal and molecular structure of a tricyclic thia-cyclol

By following a three-step procedure, the linear peptide [(RS)-2-tritylthiopropionyl]-L-phenylalanyl-L-proline (6) has been converted into the cyclic derivative (9). On the basis of spectroscopic data and X-ray crystallographic analysis, compound (9) is shown to be a this-cyclol whose tricyclic system is related to the peptidic portion of the ergot alkaloids. Properties of the new compound are compared to those of previously studied peptidic aza- and oxa-cyclols. The thiazolidinono ring of (9) adopts in the crystal an approximate envelope conformation, whereas the pyrrolidine ring assumes a half-chair conformation. The benzylic side chain of the phenylalanine residue adopts in the crystal a folded conformation which seems to be preferred even in chloroform solution.

Structural studies of azacyclols derived from linear tripeptides

N-Benzyloxycarbonyl-L-alanyl-L-phenylalanyl-L-proline p-nitrophenyl ester (4) and its N-p-bromobenzyloxycarbonyl analogue (2) each cyclize in alkaline aqueous medium to give a tricyclic system containing a free hydroxy-group derived from intramolecular addition of NH to amide carbonyl. Both the five-membered rings of the tricyclic system assume an envelope conformation. In the six-membered ring only the carbon atom bearing the cyclolic hydroxy-group is out of the plane of the other ring atoms. The benzylic side-chain of the phenylalanine residue adopts an extended conformation in both azacyclols. The crystal and molecular structures and spectral data for the tricyclic compounds (3) and (5) are reported.

Synthesis of peptides containing 1,2,3,4-tetrahydroquinoline-2-carboxylic acid. Part 2. Crystal and molecular structure of a 1H,3H,5H-oxazolo[3,4-a]quinolin-3-one derivative obtained from a linear tripeptide

Treatment of N-benzyloxycarbonyl-(S)-alanyl-(S)-phenylalanyl-(R)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid (1a) with acetic anhydride–sodium acetate gives a cyclization product (4a) containing the 1H,3H,5H-oxazolo[3,4-a]quinoline system. The structure of the bromo-derivative (4b) was examined by crystallographic and spectroscopic methods. Crystals are monoclinic, space group P21, a= 9.835, b= 26.018, c= 10.856 A, β= 93.78°, Z= 4. The structure has been refined to R 0.08 for 3 615 reflections. The two molecules found in the asymmetric unit assume slight different conformations. Some spectroscopic data for the new peptide are described in relation to the conformations found in the crystals. The mechanism of the cyclization is discussed and related to the Dakin–West reaction.