Crystal structure of (S)-2-amino-2-methyl­succinic acid

Isao Fujii

doi:10.1107/S2056989015016709

. 2015 Sep 12;71(Pt 10):o731–o732. doi: 10.1107/S2056989015016709

Crystal structure of (S)-2-amino-2-methylsuccinic acid

Isao Fujii ^a,^*

PMCID: PMC4647375 PMID: 26594447

Abstract

The title compound, C₅H₉NO₄, crystallized as a zwitterion. There is an intramolecular N—H⋯O hydrogen bond involving the trans-succinic acid and the ammonium group, forming an S(6) ring motif. In the crystal, molecules are linked by O—H⋯O hydrogen bonds, forming C(7) chains along the c-axis direction. The chains are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming sheets parallel to the bc plane. Further N—H⋯O hydrogen bonds link the sheets to form a three-dimensional framework.

Keywords: crystal structure, succinic acid, zwitterion, hydrogen bonding, three-dimensional framework

Related literature

For general background and biological properties of 2-methylaspartic acid (MeASP), see: Pfeiffer & Heinrich (1936 ▸); Delbaere et al. (1989 ▸); Nobe et al. (1998 ▸). For the absolute configuration and synthesis of the title compound, see: Terashima et al. (1966 ▸). For the crystal structure of related racemic compounds, see: Derricott et al. (1979 ▸); Brewer et al. (2013 ▸). For the crystal structure of dl-ASP, see: Flaig et al. (1998 ▸).

Experimental

Crystal data

C₅H₉NO₄
M _r = 147.13
Monoclinic,
a = 8.3398 (12) Å
b = 9.6725 (10) Å
c = 8.0671 (10) Å
β = 95.175 (5)°
V = 648.09 (14) Å³
Z = 4
Cu Kα radiation
μ = 1.14 mm⁻¹
T = 297 K
0.4 × 0.2 × 0.2 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▸) T _min = 0.76, T _max = 0.81
843 measured reflections
700 independent reflections
699 reflections with I > 2σ(I)
R _int = 0.019
3 standard reflections every 300 reflections intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.096
S = 1.27
700 reflections
109 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▸); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▸); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and Mercury (Macrae et al., 2008 ▸); software used to prepare material for publication: PLATON (Spek, 2003 ▸) and WinGX (Farrugia, 2012 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015016709/su5203sup1.cif

e-71-0o731-sup1.cif^{(150.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015016709/su5203Isup2.hkl

e-71-0o731-Isup2.hkl^{(57.9KB, hkl)}

Click here for additional data file.^{(3KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015016709/su5203Isup3.cml

Click here for additional data file.^{(223.2KB, tif)}

. DOI: 10.1107/S2056989015016709/su5203fig1.tif

A view of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The dashed line indicates the intramolecular N—H⋯O hydrogen bond (see Table 1).

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015016709/su5203fig2.tif

A partial view of the crystal packing of the title compound. Dashed lines indicate the O—H⋯O and N—H⋯O hydrogen bonds (see Table 1).

Click here for additional data file.^{(1.7MB, tif)}

c . DOI: 10.1107/S2056989015016709/su5203fig3.tif

A view along the c axis of the crystal packing of the title compound. Dashed lines indicate the O—H⋯O and N—H⋯O hydrogen bonds (see Table 1), and C-bound H atoms have been omitted for clarity.

CCDC reference: 1422827

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N1H7O4	0.79(4)	2.23(4)	2.798(3)	130(3)
O3H6O1ⁱ	0.84(4)	1.70(4)	2.543(2)	177(5)
N1H7O3ⁱⁱ	0.79(4)	2.53(4)	3.093(3)	130(3)
N1H8O2ⁱⁱⁱ	0.86(3)	1.90(4)	2.754(3)	170(3)
N1H9O1^iv	0.93(3)	1.93(4)	2.844(3)	168(4)
C3H3BO4^v	0.97	2.52	3.279(4)	135

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The author thanks Tokai University for a research grant, which partially supported this work.

supplementary crystallographic information

S1. Comment

Solid-phase synthesis is now the accepted method to synthesis peptides, in which protected natural or non-natural amino acids are widely used; for example, 2-methylaspartic acid (MeASP) a non-natural amino acid. It has attracted attention as a substrate analog of aspartate aminotransferase (EC 2.6.1.1), and acts as a competitive inhibitor in the external aldimine (Delbaere et al., 1989; Nobe et al., 1998). Despite the biological and pharmaceutical interest, no crystal structures of MeASP derivatives have been reported except for the structure of DL-MeASP monohydrate (Brewer et al., 2013).

In the title compound, Fig. 1, the succinic acid group has a trans-conformation [C1—C2—C3—C4 = -177.1 (2)°] versus. a cis-conformation [48.8 (4) °] in DL-MeASP. The carboxy group and the amino group make a hydrogen bonded half-chair S(6) ring motif (Table 1 and Fig. 1). The S(6) ring half-chair conformation and the trans-succinic acid arrangement are similar to the situation found in for DL-ASP (DLASPA03: Flaig et al. 1998).

In the crystal, molecules are linked by O—H···O hydrogen bonds, involving the succinic acid groups, to form C(7) chains along the c axis direction (Table 1 and Fig. 2). This is in contrast to the N—H···O hydrogen bonded C(5) chains observed in the crystal structure of DL-MeASP. The chains are linked by N—H···O and C—H···O hydrogen bonds forming sheets parallel to the bc plane. Further N—H···O hydrogen bonds link the sheets to form a three-dimensional framework (Table 1 and Fig. 3). The methyl groups are surrounded by the hydrophilic planes and make a columnar structure (Fig. 3).

S2. Synthesis and crystallization

The title compound was purchased from Nagase-Sangyo Co. Ltd. The absolute configuration could not be established by anomalous-dispersion effects. The (S) enantiomer has been chosen by referring the sign of known polarity in the synthetic procedure (Terashima et al., 1966). Rod-like colourless crystals of the title compound were obtained by vapour-phase diffusion of an ethanol-chloroform mixture at room temperature.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All the H atoms were located in difference Fourier maps. The NH2 and OH H atoms were freely refined. The C-bound H atoms were included in calculated positions and treated as riding atoms: C–H = 0.96-0.97 Å with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) for other H atoms.