(2S,4R)-4-Ammonio-5-oxopyrrolidine-2-carboxylate

In the crystal structure of the title compound, C5H8N2O3, the molecules exist in the zwitterionic form. The pyrrolidine ring adopts an envelope conformation with the unsubstituted endocyclic C atom situated at the flap. The other four endocyclic atoms are coplanar with the exocyclic carbonyl O atom, with an r.m.s. deviation from the mean plane of 0.06 Å. The carboxylate substituent is located axially, while the ammonium group occupies an equatorial position. In the crystal structure, the molecules are linked through N—H⋯O hydrogen bonds, forming a three-dimensional network.

Financial support from the Ministry of Science and Higher Education, Poland (project No. 2P05F00129) is gratefully acknowledged.
(2S,4R)-4-Ammonio-5-oxopyrrolidine-2-carboxylate K. Kaczmarek, J. Wojciechowski and W. M. Wolf Comment N-methyl amino acids and proline residues in the peptide chain may cause the cis-trans isomerisation of the amide bond and lead to conformational changes, which influence the molecular recognition (Dugave & Demange, 2003). Importance of the cis-amide bonds for the peptide bioactivity led to the construction of modified amino acids, which could lock a peptide bond in the cis-geometry (Dumy et al., 1997;Keller et al., 1998;Mutter et al., 1999;Tuchscherer & Mutter, 2001). In particular, Paul et al. (1992) designed mimetics of the cis-peptide bond based on the substitituted pyroglutamic acid residue. In contrast with a tetrazole replacement for the peptide bond, the pyroglutamic acid derivatives are more rigid (Zabrocki et al., 1988).
Their carboxylic group could be either donor or acceptor of hydrogen bond without invloving the polypeptide main chain amide moieties (Kaczmarek et al., 2005).
The 4-aminopyroglutamic acid is a particularly useful residue for building the conformationally restricted peptide chains.
Depending on the absolute configuration at both chiral centers it may be applied to construct the VIa or VIb β-turn mimetics.
The title compound may be obtained by two different methods elaborated by us, i.e. by electrophilic amination reaction of N-protected (S)-pyroglutamate ester, which gives separable 9:1 mixture of (2S,4R) and (2S,4S) diastereoisomers (Kaczmarek et al., 2001) or through Michael addition of dehydroalanine derivatives to sodium salt of N-benzyloxycarbonylaminomalonate ester, which gives after hydrolysis and decarboxylation mixture of all four possible stereomers. The details of the last reaction and resolution of stereoisomers will be described elsewhere (Kaczmarek, 2009).
A view of the title compound is given in Fig. 1. The molecule has two chiral centres viz. C3 and C5. Their absolute configurations follow from the synthetic procedure and are R and S, respectively.
The pyrrolidine ring adopts an envelope conformation with N1, C2, C3 and C5 almost coplanar and the C4 situated at the flap.
Additionally, the former four endocyclic atoms are coplanar with the exocyclic carbonyl oxygen, the average r.m.s. deviation from the mean plane is 0.06 Å.
In the crystal each molecule is linked through N-H ···O hydrogen bonds with eight adjacent molecules, their deatils are shown in Table 2 and Fig. 2. supplementary materials sup-2 Experimental An optically pure (ee>99%) N'-benzyloxycarbonyl protected precursor of the title compound was hydrogenated in methanol solution over 10% palladium on charcoal, which resulted in precipitation of the final product. After filtration of solids final product was washed out of the catalyst with the aim of water. The (2S,4R)-4-aminopyroglutamic acid crystals were grown from this water solution by slow evaporation.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.