Journal of Crystallographic and Spectroscopic Research, Vol. 22, No. 6, 1992 Cyclodipeptides: Structure and conformation of cyclo(tyrosyl-- prolyl) P. J. Milne, 1 D. W. Oliver, 1'* and H. M. Roos 2 Received July 3, 1991; accepted February 17, 1992 The structure and conformation of the cyclodipeptide, cyclo(Tyrosyl--Pmlyl), cyclo(Tyr--Pro) have been investigated with X-ray crystallographic and spectroscopic methods. Two conforma- tions of cyclo(Tyr--Pro) crystallized in the space group P212~2 with cell dimensions a = 11.890(3), b = 12.057(1), c = 18.528(4). Both these conformations are uncommon for cyclo- dipeptides containing a proline residue. The tyrosyl side chains of these conformers are folded towards the diketopiperazine (DKP) ring. The DKP ring adopts a flattened chair conformation in contrast to the typical boat conformation generally observed for DKP rings. The conformation of the pyrrolidine ring can be described as a pseudo C2 symmetrical twist. One intermolecular hydro- gen bond was observed for each of the two conformations of cyclo(Tyr--Pro). The hydrogen of the hydroxyl group of the tyrosyl residue is hydrogen bonded to the oxygen of the carbonyl group of the diketopiperazine ring, i.e., the carbonyl group originating from the tyrosyl residue. NMR spectroscopic studies indicated a different conformation for cyclo(Tyr--Pro) in solution similar to the generally observed conformation of cyclodipeptides, i.e., extended aromatic side chain and boat conformation for the DKP ring. Introduction Conformationally restricted peptides present sim- ple and valuable models to gain conformational insight into larger peptides and proteins and three dimensional structure-bioactivity relationships. Cyclic peptides through short-range cyclizations have during the past two decades attracted considerable attention because of their limited conformational freedom and higher prob- ability of conformational homogeneity when compared with their linear analogs (Deber et al., 1976; Toniolo, 1990). Naturally occurring cyclic peptides (2,5-dioxo- piperazines) such as sporidesmins and bicyclomin were found to exhibit antiviral and antimicrobial activities respectively (Sammes, 1975). Cyclic dipeptides are the ~ Department of Pharmaceutical Chemistry, Pretoria College of Phar- macy, University of Pretofia and Pretoria Technikon, Pretofia, 0001, Republic of South Africa. 2Department of Chemistry, University of Pretoria, Pretofia, 0001, Republic of South Africa. simplest of the cyclic peptides and have no terminal charged groups. Recently, the conformation of the cyclodipeptide, cyclo(D-phenylalanyl-trans-4-fluoro-D- Prolyl) [cyclo(Phe--fluoro--Pro)] was studied and found that the diketopiperazine (DKP) ring assumes an uncommon conformation for cyclodipeptides containing a proline residue (Ciarkowski et al., 1990). In this paper we report the synthesis, structure and spectroscopic properties of cyclo(S-Tyrosyl--S-Prolyl), cyclo (Tyr--Pro) (see Scheme 1). 643 HO Scheme 1 0277-8068/92/1200-0643506.50/0 9 1992Plenum Publishing Corporation