organic compounds
S)-2-amino-2-methylsuccinic acid
of (aSchool of Science, Tokai University, 4-1-1 Kitakaname, Hiratuka, Kanagawa 259-1292, Japan
*Correspondence e-mail: fujii@wing.ncc.u-tokai.ac.jp
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.
CCDC reference: 1422827
1. 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 and synthesis of the title compound, see: Terashima et al. (1966). For the of related racemic compounds, see: Derricott et al. (1979); Brewer et al. (2013). For the of DL-ASP, see: Flaig et al. (1998).
2. Experimental
2.1. Crystal data
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2.3. Refinement
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Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell 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).
Supporting information
CCDC reference: 1422827
10.1107/S2056989015016709/su5203sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2056989015016709/su5203Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989015016709/su5203Isup3.cml
Solid-phase synthesis is now the accepted method to synthesis
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
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).The title compound was purchased from Nagase-Sangyo Co. Ltd. The
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.Crystal data, data collection and structure
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.Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell
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).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). | |
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). | |
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. |
C5H9NO4 | F(000) = 312 |
Mr = 147.13 | Dx = 1.508 Mg m−3 |
Monoclinic, C2 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: C 2y | Cell parameters from 25 reflections |
a = 8.3398 (12) Å | θ = 20–28° |
b = 9.6725 (10) Å | µ = 1.14 mm−1 |
c = 8.0671 (10) Å | T = 297 K |
β = 95.175 (5)° | Rod, colorless |
V = 648.09 (14) Å3 | 0.4 × 0.2 × 0.2 mm |
Z = 4 |
Enraf–Nonius CAD-4 diffractometer | 699 reflections with I > 2σ(I) |
Radiation source: sealed X-ray tube | Rint = 0.019 |
Graphite monochromator | θmax = 74.0°, θmin = 5.5° |
ω/2θ scans | h = −10→1 |
Absorption correction: ψ scan (North et al., 1968) | k = −12→0 |
Tmin = 0.76, Tmax = 0.81 | l = −10→10 |
843 measured reflections | 3 standard reflections every 300 reflections |
700 independent reflections | intensity decay: none |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.034 | H 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 reflections | Δρmax = 0.29 e Å−3 |
109 parameters | Δρmin = −0.21 e Å−3 |
2 restraints | Extinction correction: SHELXL2014 (Sheldrick, 2014), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.045 (4) |
C5H9NO4 | V = 648.09 (14) Å3 |
Mr = 147.13 | Z = 4 |
Monoclinic, C2 | Cu Kα radiation |
a = 8.3398 (12) Å | µ = 1.14 mm−1 |
b = 9.6725 (10) Å | T = 297 K |
c = 8.0671 (10) Å | 0.4 × 0.2 × 0.2 mm |
β = 95.175 (5)° |
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 = 0.81 | 3 standard reflections every 300 reflections |
843 measured reflections | intensity decay: none |
700 independent reflections |
R[F2 > 2σ(F2)] = 0.034 | 2 restraints |
wR(F2) = 0.096 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.27 | Δρmax = 0.29 e Å−3 |
700 reflections | Δρmin = −0.21 e Å−3 |
109 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
H8 | 0.155 (3) | 0.434 (4) | 0.122 (4) | 0.026 (7)* | |
H7 | 0.126 (4) | 0.416 (4) | 0.275 (5) | 0.040 (9)* | |
H6 | 0.207 (5) | 0.170 (5) | 0.725 (4) | 0.071 (14)* | |
H9 | 0.022 (4) | 0.340 (4) | 0.164 (4) | 0.040 (9)* | |
C1 | 0.2417 (3) | 0.1802 (3) | 0.0388 (3) | 0.0273 (5) | |
C2 | 0.2485 (3) | 0.2608 (2) | 0.2046 (3) | 0.0238 (5) | |
C3 | 0.2132 (3) | 0.1603 (3) | 0.3436 (3) | 0.0305 (6) | |
H3A | 0.1108 | 0.1156 | 0.3124 | 0.037* | |
H3B | 0.2954 | 0.0891 | 0.3512 | 0.037* | |
C4 | 0.2069 (3) | 0.2244 (3) | 0.5137 (3) | 0.0284 (6) | |
C5 | 0.4148 (3) | 0.3267 (4) | 0.2343 (4) | 0.0386 (7) | |
H5A | 0.4277 | 0.3947 | 0.1498 | 0.058* | |
H5B | 0.4959 | 0.2567 | 0.2301 | 0.058* | |
H5C | 0.4254 | 0.3702 | 0.3417 | 0.058* | |
N1 | 0.1250 (3) | 0.3741 (2) | 0.1916 (3) | 0.0248 (5) | |
O1 | 0.1677 (2) | 0.2358 (2) | −0.0871 (2) | 0.0378 (5) | |
O2 | 0.3164 (3) | 0.0705 (2) | 0.0427 (3) | 0.0525 (7) | |
O3 | 0.2242 (3) | 0.1339 (2) | 0.6334 (2) | 0.0392 (6) | |
O4 | 0.1831 (4) | 0.3463 (2) | 0.5370 (2) | 0.0554 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0384 (11) | 0.0263 (12) | 0.0177 (10) | 0.0010 (10) | 0.0051 (8) | −0.0020 (9) |
C2 | 0.0349 (10) | 0.0220 (11) | 0.0147 (10) | 0.0029 (9) | 0.0028 (8) | −0.0013 (8) |
C3 | 0.0520 (14) | 0.0239 (13) | 0.0157 (10) | 0.0039 (11) | 0.0039 (9) | −0.0005 (9) |
C4 | 0.0436 (13) | 0.0252 (12) | 0.0164 (10) | 0.0015 (10) | 0.0025 (9) | −0.0014 (9) |
C5 | 0.0342 (12) | 0.0476 (17) | 0.0338 (13) | −0.0022 (12) | 0.0020 (10) | −0.0065 (12) |
N1 | 0.0368 (11) | 0.0213 (10) | 0.0164 (9) | 0.0008 (8) | 0.0036 (7) | −0.0007 (8) |
O1 | 0.0510 (10) | 0.0455 (11) | 0.0167 (8) | 0.0152 (9) | 0.0011 (7) | −0.0039 (8) |
O2 | 0.0930 (17) | 0.0383 (13) | 0.0257 (10) | 0.0290 (13) | 0.0023 (10) | −0.0082 (9) |
O3 | 0.0721 (13) | 0.0304 (10) | 0.0162 (9) | 0.0085 (9) | 0.0096 (8) | 0.0010 (8) |
O4 | 0.118 (2) | 0.0290 (12) | 0.0200 (9) | 0.0126 (12) | 0.0102 (10) | −0.0024 (8) |
C1—O2 | 1.229 (3) | C4—O4 | 1.213 (4) |
C1—O1 | 1.261 (3) | C4—O3 | 1.301 (3) |
C1—C2 | 1.545 (3) | C5—H5A | 0.9600 |
C2—N1 | 1.502 (3) | C5—H5B | 0.9600 |
C2—C5 | 1.525 (3) | C5—H5C | 0.9600 |
C2—C3 | 1.532 (3) | N1—H8 | 0.86 (4) |
C3—C4 | 1.511 (3) | N1—H7 | 0.78 (4) |
C3—H3A | 0.9700 | N1—H9 | 0.93 (4) |
C3—H3B | 0.9700 | O3—H6 | 0.84 (2) |
O2—C1—O1 | 126.8 (2) | O4—C4—C3 | 124.0 (2) |
O2—C1—C2 | 115.7 (2) | O3—C4—C3 | 112.8 (2) |
O1—C1—C2 | 117.3 (2) | C2—C5—H5A | 109.5 |
N1—C2—C5 | 108.3 (2) | C2—C5—H5B | 109.5 |
N1—C2—C3 | 109.79 (18) | H5A—C5—H5B | 109.5 |
C5—C2—C3 | 112.5 (2) | C2—C5—H5C | 109.5 |
N1—C2—C1 | 109.67 (18) | H5A—C5—H5C | 109.5 |
C5—C2—C1 | 107.98 (18) | H5B—C5—H5C | 109.5 |
C3—C2—C1 | 108.60 (19) | C2—N1—H8 | 107 (2) |
C4—C3—C2 | 115.4 (2) | C2—N1—H7 | 112 (3) |
C4—C3—H3A | 108.4 | H8—N1—H7 | 104 (3) |
C2—C3—H3A | 108.4 | C2—N1—H9 | 112 (3) |
C4—C3—H3B | 108.4 | H8—N1—H9 | 113 (3) |
C2—C3—H3B | 108.4 | H7—N1—H9 | 109 (3) |
H3A—C3—H3B | 107.5 | C4—O3—H6 | 111 (4) |
O4—C4—O3 | 123.2 (2) |
D—H···A | D—H | H···A | D···A | 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+1/2, y+1/2, −z+1; (iii) −x+1/2, y+1/2, −z; (iv) −x, y, −z; (v) −x+1/2, y−1/2, −z+1. |
D—H···A | D—H | H···A | D···A | 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+1/2, y+1/2, −z+1; (iii) −x+1/2, y+1/2, −z; (iv) −x, y, −z; (v) −x+1/2, y−1/2, −z+1. |
Acknowledgements
The author thanks Tokai University for a research grant, which partially supported this work.
References
Brewer, G., Burton, A. S., Dworkin, J. P. & Butcher, R. J. (2013). Acta Cryst. E69, o1856–o1857. CSD CrossRef CAS IUCr Journals Google Scholar
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. CrossRef CAS PubMed Google Scholar
Derricott, C. & Trotter, J. (1979). Acta Cryst. B35, 2230–2232. CSD CrossRef CAS IUCr Journals Google Scholar
Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Flaig, R., Koritsanszky, T., Zobel, D. & Luger, P. (1998). J. Am. Chem. Soc. 120, 2227–2238. Web of Science CSD CrossRef CAS Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
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. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Nobe, Y., Kawaguchi, S., Ura, H., Nakai, T., Hirotsu, K., Kato, R. & Kuramitsu, S. (1998). J. Biol. Chem. 273, 29554–29564. Web of Science CrossRef CAS PubMed Google Scholar
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science Google Scholar
Pfeiffer, P. & Heinrich, E. (1936). J. Prakt. Chem. 146, 105–112. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar
Terashima, S., Achiwa, K. & Yamada, S. (1966). Chem. Pharm. Bull. 14, 572–578. CrossRef CAS PubMed Google Scholar
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