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

Fujii, I.

doi:10.1107/S2056989015016709

organic compounds

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Volume 71| Part 10| October 2015| Pages o731-o732

doi:10.1107/S2056989015016709

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

Isao Fujii ^a ^*

^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.

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 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 ).

2. Experimental

2.1. Crystal data

C₅H₉NO₄
M_r = 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 ) 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

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
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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⋯O1^iv	0.93 (3)	1.93 (4)	2.844 (3)	168 (4)
C3—H3B⋯O4^v	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 ); 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).

Supporting information

CCDC reference: 1422827

Crystal structure: contains datablocks global, I. DOI: 10.1107/S2056989015016709/su5203sup1.cif

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

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

checkCIF report

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 U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(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

	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.

(S)-2-Amino-2-methylsuccinic acid top

Crystal data top

C₅H₉NO₄	F(000) = 312
M_r = 147.13	D_x = 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

Data collection top

Enraf–Nonius CAD-4 diffractometer	699 reflections with I > 2σ(I)
Radiation source: sealed X-ray tube	R_int = 0.019
Graphite monochromator	θ_max = 74.0°, θ_min = 5.5°
ω/2θ scans	h = −10→1
Absorption correction: ψ scan (North et al., 1968)	k = −12→0
T_min = 0.76, T_max = 0.81	l = −10→10
843 measured reflections	3 standard reflections every 300 reflections
700 independent reflections	intensity decay: none

Refinement top

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(F_o²) + (0.0559P)² + 0.2563P] where P = (F_o² + 2F_c²)/3
S = 1.27	(Δ/σ)_max < 0.001
700 reflections	Δρ_max = 0.29 e Å⁻³
109 parameters	Δρ_min = −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)

Crystal data top

C₅H₉NO₄	V = 648.09 (14) Å³
M_r = 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)°

Data collection top

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

Refinement top

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	Δρ_max = 0.29 e Å⁻³
700 reflections	Δρ_min = −0.21 e Å⁻³
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

	x	y	z	U_iso*/U_eq
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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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···O1^iv	0.93 (3)	1.93 (4)	2.844 (3)	168 (4)
C3—H3B···O4^v	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.

Hydrogen-bond geometry (Å, º) top

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···O1^iv	0.93 (3)	1.93 (4)	2.844 (3)	168 (4)
C3—H3B···O4^v	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.

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CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 71| Part 10| October 2015| Pages o731-o732

doi:10.1107/S2056989015016709

Open

access