N-acyl-diketopiperazines: crystal structure and conformation of N-(N-phenylacetyl-L-alanyl)-cyclo-(L-phenylalanyl-D-prolyl)

N-(N-phenylacetyl-L-alanyl)-cyclo-(L-phenylalanyl-D-prolyl) (I) was synthesized in one step starting from the linear precursor phenylacetyl-L-alanyl-L-phenyl-alanyl-L-proline. X-ray crystallographic analysis of (I) shows that the diketopiperazine ring adopts a boat conformation appreciably more puckered than that found in the unacylated cyclo(L-Pro-D-Phe). The side chain of Phe residue is in quasi-axial flagpole orientation with the aromatic ring folded over the diketopiperazine ring. 1H-n.m.r. data indicate that the same conformation is preferred in chloroform solution. The proline ring assumes a β-envelope conformation. No intramolecular interactions between the diketopiperazine system and the aromatic ring of the N-phenylacetyl-alanyl side chain have been evidenced. Crystals: space group P21 with a= 9.956(3), b= 8.809(2), c= 13.615(2) A, β= 111.0(1)° and Z = 2. The final R and Rw are 0.037 and 0.052, respectively.