Cyclo(l-tyrosyl-l-tryptophanyl) dimethylformamide solvate

The structure of the title compound [systematic name: (3S,6S)-3-(4-hydroxybenzyl)-6-(1H-indol-3-ylmethyl)piperazine-2,5-dione dimethylformamide solvate], C20H19N3O3·C3H7NO, contains hydrogen-bonded tapes typical for diketopiperazines. The structure is stabilized by strong intermolecular interactions of the types O—H⋯O and N—H⋯O involving the dipeptide and the solvent molecules. The absolute configuration was known from the starting materials.

The crystal structure of (I) contains straight hydrogen-bonded tapes as seen in (unperturbed e.g. by additional cyclic connections between the two C α -atoms). The periodicity of this pattern, usually corresponding to a unit-cell parameter, shows a quite narrow distribution with 54 out of 59 observations in the range 6.06 to 6.26 Å, with 6.19 Å observed for (I) being close to the 6.16 Å average value. The full range observed in the CSD is from 6.01 to 6.57 Å, with the upper limit being represented by a distinct outlier (piperazine-2,5-dione:2,5-dihydroxyterephatlic acid 1:1, Luo & Palmore, 2002).
The carbonyl O atom of the cocrystallized dimethylformamide (DMF) solvent molecule accepts a H atom from the Tyr hydroxyl group, but the DMF molecule is also involved in a number of weaker hydrogen bonds (Table 2 and Fig. 2). This is in line with previous findings that DMF molecules are often more heavily involved in intermolecular interactions than one traditionally would expect (Görbitz & Hersleth, 2000).
From the 20 naturally occurring amino acids one can construct 210 different cyclic dipeptides (as opposed to 400 linear dipeptides). Single crystal structural studies have been presented for 20 of them, including four structures with Tyr or Trp residues: cyclo(Gly-Trp) (Morris et al., 1974), cyclo(Trp-Trp) DMSO solvate (Grant et al., 1999), cyclo(Leu-Tyr) hydrate (Suguna et al., 1984), and cyclo(Ser-Tyr) hydrate (Lin & Webb, 1973). From a conformational point of view these four peptides resemble (I) as well as each other, and all except cyclo(Trp-Trp) crystallize in the P2 1 space group. Nevertheless, each cyclic dipeptide has its own unique packing arrangement, also when all other compounds with a diketopiperazine moiety are considered.

S2. Experimental
The corresponding linear peptide Tyr-Trp was obtained from Bachem. Crystals of the cyclic analogue resulting from ring closure were obtained by slow evaporation of a solution of Tyr-Trp in dimethylformamide.

S3. Refinement
Positional parameters were refined for H atoms involved in short hydrogen bonds. Other H atoms were positioned with idealized geometry and fixed C-H distances for CH 3 , CH 2 , CH and aromatic CH type H-atoms at 0.98, 0.99, 1.00 and 0.95 Å, respectively; U iso values were 1.2U eq of the carrier atom or 1.5U eq for the OH and methyl groups. In the absence supporting information sup-2 Acta Cryst. (2008). E64, o436 of significant anomalous scattering effects, 2334 Friedel pairs were merged. The absolute configuration was known for the purchased material.