rac-3-exo-Ammonio-7-anti-carb­oxy­tricyclo­[2.2.1.0.2,6]heptane-3-endo-carboxyl­ate monohydrate

Graham Smith; Urs D Wermuth; Ian D Jenkins

doi:10.1107/S1600536812016236

. 2012 Apr 21;68(Pt 5):o1468–o1469. doi: 10.1107/S1600536812016236

rac-3-exo-Ammonio-7-anti-carboxytricyclo[2.2.1.0.^2,6]heptane-3-endo-carboxylate monohydrate

Graham Smith ^a,^*, Urs D Wermuth ^b, Ian D Jenkins ^c

PMCID: PMC3344580 PMID: 22590342

Abstract

The racemic title compound, C₉H₁₁NO₄·H₂O, a tricyclic rearranged aminonorbornane dicarboxylic acid, is a conformationally rigid analogue of glutamic acid and exists as an ammonium-carboxylate zwitterion, with the bridghead carboxylic acid group anti-related. In the crystal, N—H⋯O and O—H⋯O hydrogen bonds involving the ammonium, carboxylic acid and water donor groups with both water and carboxyl O-atom acceptors give a three-dimensional framework structure.

Related literature

For background to G-protein receptors, see: Liu & Doller (2011 ▶). For the Strecher and Bucherer–Bergs reactions, see: Strecher (1850 ▶); Bucherer & Steiner (1934 ▶). For the synthesis of aminonorbornane carboxylic acids, see: Apgar & Ludwig (1972 ▶); Tager & Christensen (1972 ▶); Wermuth (1995 ▶). For the chemistry of hydantoins, see: Avendaño López & González Trigo (1985 ▶). For the structure of a similar monocarboxylic acid tricyclic cage compound, see: Fortier et al. (1979 ▶). For graph-set analysis, see: Etter et al. (1990 ▶).

Experimental

Crystal data

C₉H₁₁NO₄·H₂O
M _r = 215.20
Monoclinic,
a = 7.7565 (2) Å
b = 11.4103 (2) Å
c = 10.3339 (3) Å
β = 94.888 (2)°
V = 911.27 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 223 K
0.30 × 0.30 × 0.15 mm

Data collection

Oxford Diffraction Gemini-S Ultra CCD-detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010 ▶) T _min = 0.990, T _max = 1.000
7572 measured reflections
2128 independent reflections
1589 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.091
S = 0.97
2128 reflections
160 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) within WinGX (Farrugia, 1999 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812016236/lh5454sup1.cif

e-68-o1468-sup1.cif^{(22.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812016236/lh5454Isup2.hkl

e-68-o1468-Isup2.hkl^{(102.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812016236/lh5454Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1W—H11W⋯O71ⁱ	0.90 (2)	2.02 (2)	2.9161 (16)	176 (2)
O1W—H12W⋯O31ⁱⁱ	0.93 (2)	1.77 (2)	2.6792 (16)	168 (2)
N31—H31A⋯O31ⁱⁱ	0.94 (2)	1.87 (2)	2.7712 (17)	161 (2)
N31—H31B⋯O71ⁱⁱⁱ	0.91 (2)	2.29 (2)	3.1261 (17)	153.0 (15)
N31—H31B⋯O72ⁱⁱⁱ	0.91 (2)	2.27 (2)	3.0720 (17)	147.6 (15)
N31—H31C⋯O32^iv	0.874 (18)	1.925 (17)	2.7769 (16)	164.4 (17)
O72—H72⋯O1W	0.94 (3)	1.60 (3)	2.5282 (16)	174 (3)

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

Acknowledgments

The authors acknowledge financial support from the Australian Research Council, the Science and Engineering Faculty and the University Library, Queensland University of Technology and Griffith University.

supplementary crystallographic information

Comment

G-protein-coupled receptors (GPCRs) constitute a superfamily of proteins whose main function is to convert extracellular stimuli into intracellular signals (Liu & Doller, 2011). Metabotropic glutamate (mGu) receptors belong to the class C GPCR group and are activated by L-glutamate. The title compound, C₉H₁₁NO₄. H₂O (I), is a hydrated tricyclic rearranged aminonorbornane dicarboxylic acid cage compound which is a conformationally rigid analogue of glutamic acid, and was synthesized as a potential ligand for metabotropic glutamate receptors in order to explore the requirements for activity at these receptors (Wermuth, 1995). For the synthesis of amino-substituted norbornane carboxylic acids, see also Tager & Christensen (1972) and Apgar & Ludwig (1972).

The title compound exists as an ammonium carboxylate zwitterion with the C3 carboxylate group endo-oriented (Fig. 1). Note that the stereochemical assignment of exo and endo on such nortricyclic systems is somewhat arbitrary and depends on how the system is drawn. The carboxylic acid group at C7 in (I) is exo and has the acid H-atom (H72) anti-located, forming a hydrogen bond with the water molecule of solvation (Table 1). This water molecule gives intermolecular hydrogen-bonding associations with carboxyl O-atom acceptors, while the ammonium group also forms four hydrogen bonds with carboxyl O-atom acceptors. These include a symmetric cyclic N—H···O,O' head-to-tail association [graph set R²₁(4) (Etter et al., 1990)] which links the molecules along (100). Overall, a three-dimensional framework structure is formed (Fig. 2).

The structures of similar tricyclic norbornane compounds are rare in the crystallographic literature. The nortricyclic keto acid which served as the precursor to (IV) in the synthesis of (I) (Fig. 3) is known (Fortier et al., 1979).

Experimental

The title compound (I) was synthesized (Wermuth, 1995) by the hydrolysis with Ba(OH)₂ of the diasteroisomeric hydantoin mixture (II), which was obtained by a Read synthesis (Avendaño López & González Trigo, 1985) performed on the nortricyclic keto-ester (IV) (Fig. 3). Briefly, a Strecker aminonitrile (Streker, 1850) is formed in the usual manner (50% yield) and this was converted to a hydrochloride (III) and reacted with KOCN in an acetic acid–water mixture at 273K for 1 h followed by the addition of conc. HCl and heating for a further 15 min at 273K. The product was a diastereomeric mixture of hydantoins in 49% yield after recrystallization from 50% aqueous ethanol. The stereochemistry of the amino acid moiety is the inverse (carboxylic acid group exo) of that normally formed in the Bucherer-Bergs reaction (Bucherer & Steiner, 1934). The colourless product obtained gave an elemental analysis consistent with a 0.25 hydrate but recrystallization from various solvents gave no crystals suitable for X-ray analysis. However, colourless plates of a monohydrate (I) were obtained from the attempted reaction of this partial hydrate with picrylsulfonic acid in 80% propan-2-ol-water and a specimen suitable for the X-ray analysis was cleaved from a larger crystal.