organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890
Volume 71| Part 10| October 2015| Pages o731-o732

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

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aSchool of Science, Tokai University, 4-1-1 Kitakaname, Hiratuka, Kanagawa 259-1292, Japan
*Correspondence e-mail: fujii@wing.ncc.u-tokai.ac.jp

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 3 September 2015; accepted 7 September 2015; online 12 September 2015)

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.

1. Related literature

For general background and biological properties of 2-methyl­aspartic acid (MeASP), see: Pfeiffer & Heinrich (1936[Pfeiffer, P. & Heinrich, E. (1936). J. Prakt. Chem. 146, 105-112.]); Delbaere et al. (1989[Delbaere, L. T., Kallen, J., Markovic-Housley, Z., Khomutov, A. R., Khomutov, R. M., Karpeisky, M. Y. & Jansonius, J. N. (1989). Biochimie, 71, 449-459.]); Nobe et al. (1998[Nobe, Y., Kawaguchi, S., Ura, H., Nakai, T., Hirotsu, K., Kato, R. & Kuramitsu, S. (1998). J. Biol. Chem. 273, 29554-29564.]). For the absolute configuration and synthesis of the title compound, see: Terashima et al. (1966[Terashima, S., Achiwa, K. & Yamada, S. (1966). Chem. Pharm. Bull. 14, 572-578.]). For the crystal structure of related racemic compounds, see: Derricott et al. (1979[Derricott, C. & Trotter, J. (1979). Acta Cryst. B35, 2230-2232.]); Brewer et al. (2013[Brewer, G., Burton, A. S., Dworkin, J. P. & Butcher, R. J. (2013). Acta Cryst. E69, o1856-o1857.]). For the crystal structure of DL-ASP, see: Flaig et al. (1998[Flaig, R., Koritsanszky, T., Zobel, D. & Luger, P. (1998). J. Am. Chem. Soc. 120, 2227-2238.]).

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C5H9NO4

  • Mr = 147.13

  • Monoclinic, C 2

  • 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

2.2. Data collection

  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.76, Tmax = 0.81

  • 843 measured reflections

  • 700 independent reflections

  • 699 reflections with I > 2σ(I)

  • Rint = 0.019

  • 3 standard reflections every 300 reflections intensity decay: none

2.3. Refinement

  • R[F2 > 2σ(F2)] = 0.034

  • wR(F2) = 0.096

  • S = 1.27

  • 700 reflections

  • 109 parameters

  • 2 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.29 e Å−3

  • Δρmin = −0.21 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H7⋯O4 0.79 (4) 2.23 (4) 2.798 (3) 130 (3)
O3—H6⋯O1i 0.84 (4) 1.70 (4) 2.543 (2) 177 (5)
N1—H7⋯O3ii 0.79 (4) 2.53 (4) 3.093 (3) 130 (3)
N1—H8⋯O2iii 0.86 (3) 1.90 (4) 2.754 (3) 170 (3)
N1—H9⋯O1iv 0.93 (3) 1.93 (4) 2.844 (3) 168 (4)
C3—H3B⋯O4v 0.97 2.52 3.279 (4) 135
Symmetry codes: (i) x, y, z+1; (ii) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+1]; (iii) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z]; (iv) -x, y, -z; (v) [-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+1].

Data collection: CAD-4 Software (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]); software used to prepare material for publication: PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]) and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Supporting information


Comment top

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).

Synthesis and crystallization top

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.

Refinement top

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 Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for other H atoms.

Related literature top

For general background and biological properties of 2-methylaspartic acid (MeASP), see: Pfeiffer & Heinrich et al. (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).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (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).

Figures top
[Figure 1] Fig. 1. 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).
[Figure 2] Fig. 2. 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).
[Figure 3] Fig. 3. 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.
(S)-2-Amino-2-methylsuccinic acid top
Crystal data top
C5H9NO4F(000) = 312
Mr = 147.13Dx = 1.508 Mg m3
Monoclinic, C2Cu Kα radiation, λ = 1.54178 Å
Hall symbol: C 2yCell parameters from 25 reflections
a = 8.3398 (12) Åθ = 20–28°
b = 9.6725 (10) ŵ = 1.14 mm1
c = 8.0671 (10) ÅT = 297 K
β = 95.175 (5)°Rod, colorless
V = 648.09 (14) Å30.4 × 0.2 × 0.2 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer
699 reflections with I > 2σ(I)
Radiation source: sealed X-ray tubeRint = 0.019
Graphite monochromatorθmax = 74.0°, θmin = 5.5°
ω/2θ scansh = 101
Absorption correction: ψ scan
(North et al., 1968)
k = 120
Tmin = 0.76, Tmax = 0.81l = 1010
843 measured reflections3 standard reflections every 300 reflections
700 independent reflections intensity decay: none
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.034H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.096 w = 1/[σ2(Fo2) + (0.0559P)2 + 0.2563P]
where P = (Fo2 + 2Fc2)/3
S = 1.27(Δ/σ)max < 0.001
700 reflectionsΔρmax = 0.29 e Å3
109 parametersΔρmin = 0.21 e Å3
2 restraintsExtinction correction: SHELXL2014 (Sheldrick, 2014), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.045 (4)
Crystal data top
C5H9NO4V = 648.09 (14) Å3
Mr = 147.13Z = 4
Monoclinic, C2Cu Kα radiation
a = 8.3398 (12) ŵ = 1.14 mm1
b = 9.6725 (10) ÅT = 297 K
c = 8.0671 (10) Å0.4 × 0.2 × 0.2 mm
β = 95.175 (5)°
Data collection top
Enraf–Nonius CAD-4
diffractometer
699 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)
Rint = 0.019
Tmin = 0.76, Tmax = 0.813 standard reflections every 300 reflections
843 measured reflections intensity decay: none
700 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0342 restraints
wR(F2) = 0.096H atoms treated by a mixture of independent and constrained refinement
S = 1.27Δρmax = 0.29 e Å3
700 reflectionsΔρmin = 0.21 e Å3
109 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
H80.155 (3)0.434 (4)0.122 (4)0.026 (7)*
H70.126 (4)0.416 (4)0.275 (5)0.040 (9)*
H60.207 (5)0.170 (5)0.725 (4)0.071 (14)*
H90.022 (4)0.340 (4)0.164 (4)0.040 (9)*
C10.2417 (3)0.1802 (3)0.0388 (3)0.0273 (5)
C20.2485 (3)0.2608 (2)0.2046 (3)0.0238 (5)
C30.2132 (3)0.1603 (3)0.3436 (3)0.0305 (6)
H3A0.11080.11560.31240.037*
H3B0.29540.08910.35120.037*
C40.2069 (3)0.2244 (3)0.5137 (3)0.0284 (6)
C50.4148 (3)0.3267 (4)0.2343 (4)0.0386 (7)
H5A0.42770.39470.14980.058*
H5B0.49590.25670.23010.058*
H5C0.42540.37020.34170.058*
N10.1250 (3)0.3741 (2)0.1916 (3)0.0248 (5)
O10.1677 (2)0.2358 (2)0.0871 (2)0.0378 (5)
O20.3164 (3)0.0705 (2)0.0427 (3)0.0525 (7)
O30.2242 (3)0.1339 (2)0.6334 (2)0.0392 (6)
O40.1831 (4)0.3463 (2)0.5370 (2)0.0554 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0384 (11)0.0263 (12)0.0177 (10)0.0010 (10)0.0051 (8)0.0020 (9)
C20.0349 (10)0.0220 (11)0.0147 (10)0.0029 (9)0.0028 (8)0.0013 (8)
C30.0520 (14)0.0239 (13)0.0157 (10)0.0039 (11)0.0039 (9)0.0005 (9)
C40.0436 (13)0.0252 (12)0.0164 (10)0.0015 (10)0.0025 (9)0.0014 (9)
C50.0342 (12)0.0476 (17)0.0338 (13)0.0022 (12)0.0020 (10)0.0065 (12)
N10.0368 (11)0.0213 (10)0.0164 (9)0.0008 (8)0.0036 (7)0.0007 (8)
O10.0510 (10)0.0455 (11)0.0167 (8)0.0152 (9)0.0011 (7)0.0039 (8)
O20.0930 (17)0.0383 (13)0.0257 (10)0.0290 (13)0.0023 (10)0.0082 (9)
O30.0721 (13)0.0304 (10)0.0162 (9)0.0085 (9)0.0096 (8)0.0010 (8)
O40.118 (2)0.0290 (12)0.0200 (9)0.0126 (12)0.0102 (10)0.0024 (8)
Geometric parameters (Å, º) top
C1—O21.229 (3)C4—O41.213 (4)
C1—O11.261 (3)C4—O31.301 (3)
C1—C21.545 (3)C5—H5A0.9600
C2—N11.502 (3)C5—H5B0.9600
C2—C51.525 (3)C5—H5C0.9600
C2—C31.532 (3)N1—H80.86 (4)
C3—C41.511 (3)N1—H70.78 (4)
C3—H3A0.9700N1—H90.93 (4)
C3—H3B0.9700O3—H60.84 (2)
O2—C1—O1126.8 (2)O4—C4—C3124.0 (2)
O2—C1—C2115.7 (2)O3—C4—C3112.8 (2)
O1—C1—C2117.3 (2)C2—C5—H5A109.5
N1—C2—C5108.3 (2)C2—C5—H5B109.5
N1—C2—C3109.79 (18)H5A—C5—H5B109.5
C5—C2—C3112.5 (2)C2—C5—H5C109.5
N1—C2—C1109.67 (18)H5A—C5—H5C109.5
C5—C2—C1107.98 (18)H5B—C5—H5C109.5
C3—C2—C1108.60 (19)C2—N1—H8107 (2)
C4—C3—C2115.4 (2)C2—N1—H7112 (3)
C4—C3—H3A108.4H8—N1—H7104 (3)
C2—C3—H3A108.4C2—N1—H9112 (3)
C4—C3—H3B108.4H8—N1—H9113 (3)
C2—C3—H3B108.4H7—N1—H9109 (3)
H3A—C3—H3B107.5C4—O3—H6111 (4)
O4—C4—O3123.2 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H7···O40.79 (4)2.23 (4)2.798 (3)130 (3)
O3—H6···O1i0.84 (4)1.70 (4)2.543 (2)177 (5)
N1—H7···O3ii0.79 (4)2.53 (4)3.093 (3)130 (3)
N1—H8···O2iii0.86 (3)1.90 (4)2.754 (3)170 (3)
N1—H9···O1iv0.93 (3)1.93 (4)2.844 (3)168 (4)
C3—H3B···O4v0.972.523.279 (4)135
Symmetry codes: (i) x, y, z+1; (ii) x+1/2, y+1/2, z+1; (iii) x+1/2, y+1/2, z; (iv) x, y, z; (v) x+1/2, y1/2, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H7···O40.79 (4)2.23 (4)2.798 (3)130 (3)
O3—H6···O1i0.84 (4)1.70 (4)2.543 (2)177 (5)
N1—H7···O3ii0.79 (4)2.53 (4)3.093 (3)130 (3)
N1—H8···O2iii0.86 (3)1.90 (4)2.754 (3)170 (3)
N1—H9···O1iv0.93 (3)1.93 (4)2.844 (3)168 (4)
C3—H3B···O4v0.972.523.279 (4)135
Symmetry codes: (i) x, y, z+1; (ii) x+1/2, y+1/2, z+1; (iii) x+1/2, y+1/2, z; (iv) x, y, z; (v) x+1/2, y1/2, z+1.
 

Acknowledgements

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

References

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ISSN: 2056-9890
Volume 71| Part 10| October 2015| Pages o731-o732
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