Ranunculin

In the title mol­ecule {systematic name: (5S)-5-[(β-D-gluco­pyranos­yloxy)meth­yl]furan-2(5H)-one}, C₁₁H₁₆O₈, the five-membered ring is essentially planar, the maximum deviation being 0.0151 (13) Å for the O atom. The six-membered ring adopts a chair conformation with puckering parameters Q = 0.581 (2) Å, θ = 9.0 (2)° and φ = 39.7 (13)°, and with all of the substituents of the glucoside unit having normal equatorial orientations. The crystal structure is stabilized by extensive O—H...O and C—H...O hydrogen bonding, resulting in a three-dimensional network.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.026
• wR factor = 0.069
• Data-to-parameter ratio = 6.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       6.16
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          5
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.595         10
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          3

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.00
           From the CIF: _reflns_number_total               1133
           Count of symmetry unique reflns         1148
           Completeness (_total/calc)             98.69%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_4_G Note: The Model has Chirality at C5     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C6     (Verify)          R
PLAT791_ALERT_4_G Note: The Model has Chirality at C7     (Verify)          R
PLAT791_ALERT_4_G Note: The Model has Chirality at C8     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C9     (Verify)          S
PLAT791_ALERT_4_G Note: The Model has Chirality at C10    (Verify)          R

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   7 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   4 ALERT type 3 Indicator that the structure quality may be low
   7 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Ranunculin (I) is the glycosidic precursor of the vesicant protoanemonin present in numerous species of Rannunculaceae and is especially associated with the burning sensation on chewing leaves of buttercup plants. It was first obtained in crystalline form by Hill and van Heyningen (1951) who established its gross structure and showed that it undergoes enzymatic cleavage by β-glucosidase to yield the aglucone, which underwent easy dehydration to protoanemonin. These processes were shown to occur readily under autolytic conditions (Bai et al., 1996). The S-stereochemistry of the dihydrofuranone ring was deduced by Benn and Yelland (1968), and Boll (1968), as shown in the schematic diagram, and later confirmed by synthesis (Camps et al., 1982; Fang et al., 1989). Our sample of (I) was a natural product, and as such had been biosynthesised in the plant (and not made in a laboratory). The only stereoisomer which occurs naturally is the D-isomer, and both that and the anomeric configuration of the glycoosidic bond in (I) were established by cleavage of the glycoside by β-D-glucosidases. The X-ray structure reported here provides the simplest unequivocal proof of that stereochemistry since the chirality follows from that of the D-glucopyranosyl moiety.

The molecular structure of (I) is presented in Fig. 1. The five membered ring, O1/C2—C5, is essentially planar with the maximum deviation of any atom being 0.0151 (13) Å for O1. The six-membered ring adopts a chair conformation with puckering parameters (Cremer & Pople, 1975): Q = 0.581 (2) Å, θ = 9.0 (2)° and ϕ = 39.7 (13)°, with all of the substituents of the glucoside unit having normal equatorial orientations. The 5-membered ring folds back away from the six-membered ring as reflected by the torsion angle C6—O3—C1—C5 -162.86 (17)°. The bond distances and angles are as expected (Allen, 2002). The structure is stabilized by extensive O—H···O and C—H···O hydrogen bonding resulting in a three diemsional network (Table 1 & Fig. 2).

There are two other, closely related, simple butenolides known, though their structures rest on chemical and spectrometric data, i.e., without X-ray crystallographic support. They are the (5R,6R) and (5S,6R) steeroisomers of 5-([1-β-D-glucopyranosyloxy]ethyl)-2(5H)-furanone (Perry et al., 1996); the glycosidic precursor of (Z)-5-ethylidene-2(5H)-furanone, a homologue of protoanemonin in Halocarpus biformis juvenile foliage.

Related literature

For background to ranunculin, see: Hill & van Heyningen (1951); Bai et al. (1996); Benn & Yelland (1968); Boll (1968); Camps et al. (1982); Fang et al. (1989). For chemical and spectrometric data for closely related, simple butenolides, see: Perry et al. (1996). For comparison of bond distances and angles, see: Allen et al. (1987). For puckering parameters, see: Cremer & Pople (1975).

S2. Experimental

The details of the isolation, and some of the physical properties, of our sample of (I) have been reported previously (Benn & Yelland 1968). Suitable crystals of the title compound for X-ray study were grown from a solution in aqueous ethanol (ca 1:20) in the form of plates.

S3. Refinement

An absolute structure could not be established reliably because of insufficient anomalous scattering effects. Therefore, 792 Friedel pairs were merged. The H-atoms were located from difference maps and were included in the refinements at geometrically idealized positions with C—H distances = 0.95, 0.99 and 1.00 Å for aryl, methylene and methine type H-atoms, respectively; the positions of hydroxyl H-atoms were allowed to refine freely. The H-atoms were assigned U_iso = 1.2 and 1.5 × U_eq of the parent C and O-atoms, respectively. The final difference map was free of chemically significant features.

Computing details

Data collection: COLLECT (Hooft, 1998); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. ORTEP-3 (Farrugia, 1997) drawing of the title compound with displacement ellipsoids plotted at 50% probability level.
	Fig. 2. Unit cell packing of the title compound showing intermolecular hydrogen bonds of O—H···O; H-atoms not involved in hydrogen bonds have been excluded.

(5S)-5-[(β-D-glucopyranosyloxy)methyl]furan-2(5H)-one

Crystal data

C11H16O8	F(000) = 292
Mr = 276.24	Dx = 1.531 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1560 reflections
a = 5.7944 (4) Å	θ = 1.0–30.0°
b = 6.9359 (3) Å	µ = 0.13 mm^−1
c = 15.0491 (10) Å	T = 173 K
β = 97.895 (2)°	Plate, colorless
V = 599.08 (6) Å^3	0.30 × 0.24 × 0.02 mm
Z = 2

Data collection

Nonius APEXII CCD [APEXII is a Bruker machine - is this a KappaCCD upgraded with an APEXII CCD?] diffractometer	1133 independent reflections
Radiation source: fine-focus sealed tube	1112 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.018
ϕ & ω scans	θmax = 25.0°, θmin = 3.2°
Absorption correction: multi-scan (SORTAV; Blessing, 1997)	h = −6→6
Tmin = 0.961, Tmax = 0.997	k = −6→8
1926 measured reflections	l = −17→17

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.026	Hydrogen site location: difference Fourier map
wR(F^2) = 0.069	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ^2(Fo^2) + (0.040P)^2 + 0.1617P] where P = (Fo^2 + 2Fc^2)/3
1133 reflections	(Δ/σ)max = 0.002
184 parameters	Δρmax = 0.18 e Å^−3
1 restraint	Δρmin = −0.16 e Å^−3

Special details

Experimental. NMR data (400 MHz, ¹H; 100 MHz ¹³C) for a solution in D₂O containing sodium 3-trimethylsilylpropionate-2,3 - d₄ as reference: δ_H (400 MHz) 7.77 (1H, dd, J = 1.5 and 5.8 Hz, H-4), 6.3 (1H, dd, J = 2.1 and 5.8 Hz, H-3), 5.47 (1H, m), 4.48 (1H, d, J = 7.9 Hz, H-1'), 4.30 (1H, dd, J = 3.2 and 12.2 Hz, H-6 A), 3.95 (1H, dd, J = 5.8 and 12.2 Hz, H-6B), 3.91 (1H, dd, J = 2.1 and 12.5 Hz, H-6A'), 3.72 (1H, dd, J = 5.8 and 12.5 Hz, H-6B'), 3.48 (1H, dd, dd, J = ca 9 Hz H-3'), 3.43 (1H, m, H-5'), 3.37 (1H, dd, J = ca 9 Hz, H=4'), and 3.25 (1H, dd, J = 7.9 and 9.2 Hz, H-2'); δ_C 179.2 s (C-2), 158.5 d (C-4), 124.7 d (C-3), 105.6 d (C-1'), 86.9 d (C-5), 78.7 d (C-5'), 78.3 d (C-3'), 75.6 d (C-2'), 72.2 d (C-4'), 71.7 t (C-6), 63.3 t (C-6').

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.9146 (3)	−0.1112 (2)	0.96815 (9)	0.0225 (4)
O2	1.0618 (3)	−0.0493 (3)	1.11025 (10)	0.0309 (4)
O3	0.4499 (2)	0.0377 (2)	0.79524 (9)	0.0200 (3)
O4	0.5209 (2)	0.3269 (2)	0.73224 (9)	0.0188 (3)
O5	0.1227 (3)	−0.0568 (2)	0.63887 (10)	0.0241 (4)
H5O	0.085 (5)	−0.121 (5)	0.6833 (19)	0.036*
O6	−0.0241 (2)	0.2692 (2)	0.53178 (10)	0.0208 (4)
H6O	−0.025 (5)	0.336 (5)	0.479 (2)	0.031*
O7	0.3667 (3)	0.5126 (3)	0.50561 (9)	0.0215 (3)
H7O	0.259 (5)	0.591 (5)	0.4895 (18)	0.032*
O8	0.8805 (3)	0.6376 (3)	0.72096 (10)	0.0277 (4)
H8O	0.893 (5)	0.563 (5)	0.769 (2)	0.042*
C1	0.6798 (3)	0.0332 (4)	0.84401 (13)	0.0216 (5)
H1A	0.7191	0.1601	0.8721	0.026*
H1B	0.7947	0.0036	0.8030	0.026*
C2	0.8918 (4)	−0.0724 (3)	1.05518 (13)	0.0225 (5)
C3	0.6434 (4)	−0.0666 (4)	1.06406 (14)	0.0252 (5)
H3	0.5794	−0.0486	1.1183	0.030*
C4	0.5229 (4)	−0.0912 (3)	0.98301 (14)	0.0243 (5)
H4	0.3578	−0.0895	0.9699	0.029*
C5	0.6862 (4)	−0.1216 (3)	0.91570 (13)	0.0204 (5)
H5	0.6609	−0.2517	0.8874	0.025*
C6	0.4469 (4)	0.1343 (3)	0.71336 (13)	0.0178 (4)
H6	0.5552	0.0694	0.6765	0.021*
C7	0.2004 (3)	0.1338 (3)	0.66293 (13)	0.0176 (4)
H7	0.0906	0.1980	0.6994	0.021*
C8	0.2093 (3)	0.2433 (3)	0.57590 (13)	0.0167 (4)
H8	0.2985	0.1652	0.5363	0.020*
C9	0.3238 (3)	0.4413 (3)	0.59065 (13)	0.0172 (4)
H9	0.2164	0.5310	0.6170	0.021*
C10	0.5559 (3)	0.4305 (3)	0.65204 (13)	0.0180 (4)
H10	0.6738	0.3622	0.6208	0.022*
C11	0.6423 (4)	0.6302 (3)	0.67948 (14)	0.0218 (5)
H11A	0.6248	0.7137	0.6256	0.026*
H11B	0.5424	0.6840	0.7217	0.026*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0203 (7)	0.0294 (9)	0.0169 (7)	0.0038 (6)	−0.0002 (5)	0.0024 (6)
O2	0.0327 (8)	0.0329 (10)	0.0233 (8)	0.0036 (8)	−0.0095 (7)	−0.0014 (8)
O3	0.0212 (7)	0.0242 (8)	0.0137 (7)	−0.0011 (7)	−0.0005 (5)	0.0038 (6)
O4	0.0226 (7)	0.0190 (8)	0.0143 (7)	−0.0026 (6)	0.0005 (5)	−0.0001 (6)
O5	0.0317 (8)	0.0223 (8)	0.0172 (7)	−0.0077 (7)	−0.0007 (6)	0.0020 (7)
O6	0.0177 (7)	0.0259 (8)	0.0174 (7)	−0.0007 (6)	−0.0027 (6)	0.0030 (7)
O7	0.0218 (7)	0.0257 (8)	0.0172 (7)	0.0016 (7)	0.0036 (6)	0.0063 (7)
O8	0.0262 (8)	0.0330 (9)	0.0227 (8)	−0.0102 (8)	−0.0010 (6)	0.0034 (8)
C1	0.0200 (10)	0.0262 (12)	0.0175 (10)	−0.0020 (10)	−0.0010 (8)	0.0041 (9)
C2	0.0302 (11)	0.0188 (10)	0.0175 (9)	0.0063 (10)	0.0000 (9)	0.0026 (9)
C3	0.0306 (11)	0.0257 (11)	0.0201 (10)	0.0037 (10)	0.0064 (8)	0.0025 (10)
C4	0.0235 (10)	0.0234 (12)	0.0264 (12)	0.0004 (10)	0.0044 (9)	0.0071 (10)
C5	0.0217 (10)	0.0214 (11)	0.0168 (10)	−0.0001 (9)	−0.0023 (8)	0.0016 (9)
C6	0.0216 (10)	0.0179 (10)	0.0138 (9)	−0.0003 (9)	0.0020 (7)	0.0016 (9)
C7	0.0190 (10)	0.0188 (10)	0.0151 (9)	−0.0014 (9)	0.0025 (7)	0.0003 (9)
C8	0.0152 (10)	0.0207 (10)	0.0135 (9)	0.0003 (9)	−0.0001 (8)	−0.0008 (8)
C9	0.0185 (10)	0.0191 (10)	0.0143 (9)	0.0010 (9)	0.0038 (7)	0.0010 (9)
C10	0.0180 (10)	0.0216 (10)	0.0147 (9)	−0.0004 (10)	0.0038 (8)	0.0017 (9)
C11	0.0253 (11)	0.0206 (11)	0.0189 (10)	−0.0016 (9)	0.0004 (8)	0.0006 (10)

Geometric parameters (Å, º)

O1—C2	1.361 (2)	C2—C3	1.464 (3)
O1—C5	1.447 (2)	C3—C4	1.331 (3)
O2—C2	1.208 (3)	C3—H3	0.9500
O3—C6	1.401 (2)	C4—C5	1.493 (3)
O3—C1	1.430 (2)	C4—H4	0.9500
O4—C6	1.419 (3)	C5—H5	1.0000
O4—C10	1.443 (2)	C6—C7	1.523 (3)
O5—C7	1.427 (3)	C6—H6	1.0000
O5—H5O	0.86 (3)	C7—C8	1.521 (3)
O6—C8	1.434 (2)	C7—H7	1.0000
O6—H6O	0.92 (3)	C8—C9	1.528 (3)
O7—C9	1.425 (2)	C8—H8	1.0000
O7—H7O	0.84 (3)	C9—C10	1.525 (2)
O8—C11	1.435 (3)	C9—H9	1.0000
O8—H8O	0.88 (3)	C10—C11	1.511 (3)
C1—C5	1.519 (3)	C10—H10	1.0000
C1—H1A	0.9900	C11—H11A	0.9900
C1—H1B	0.9900	C11—H11B	0.9900
C2—O1—C5	109.40 (15)	O4—C6—H6	109.9
C6—O3—C1	111.09 (15)	C7—C6—H6	109.9
C6—O4—C10	112.00 (15)	O5—C7—C8	106.92 (16)
C7—O5—H5O	113 (2)	O5—C7—C6	111.72 (17)
C8—O6—H6O	110.7 (18)	C8—C7—C6	106.69 (16)
C9—O7—H7O	105.7 (19)	O5—C7—H7	110.5
C11—O8—H8O	107 (2)	C8—C7—H7	110.5
O3—C1—C5	108.08 (17)	C6—C7—H7	110.5
O3—C1—H1A	110.1	O6—C8—C7	108.63 (16)
C5—C1—H1A	110.1	O6—C8—C9	108.56 (17)
O3—C1—H1B	110.1	C7—C8—C9	112.90 (16)
C5—C1—H1B	110.1	O6—C8—H8	108.9
H1A—C1—H1B	108.4	C7—C8—H8	108.9
O2—C2—O1	120.56 (19)	C9—C8—H8	108.9
O2—C2—C3	130.8 (2)	O7—C9—C10	108.24 (15)
O1—C2—C3	108.66 (17)	O7—C9—C8	107.89 (16)
C4—C3—C2	108.1 (2)	C10—C9—C8	111.93 (17)
C4—C3—H3	125.9	O7—C9—H9	109.6
C2—C3—H3	125.9	C10—C9—H9	109.6
C3—C4—C5	109.8 (2)	C8—C9—H9	109.6
C3—C4—H4	125.1	O4—C10—C11	107.91 (16)
C5—C4—H4	125.1	O4—C10—C9	108.49 (15)
O1—C5—C4	103.91 (16)	C11—C10—C9	110.63 (17)
O1—C5—C1	106.48 (16)	O4—C10—H10	109.9
C4—C5—C1	115.19 (19)	C11—C10—H10	109.9
O1—C5—H5	110.3	C9—C10—H10	109.9
C4—C5—H5	110.3	O8—C11—C10	114.47 (18)
C1—C5—H5	110.3	O8—C11—H11A	108.6
O3—C6—O4	107.90 (15)	C10—C11—H11A	108.6
O3—C6—C7	109.54 (16)	O8—C11—H11B	108.6
O4—C6—C7	109.80 (16)	C10—C11—H11B	108.6
O3—C6—H6	109.9	H11A—C11—H11B	107.6
C6—O3—C1—C5	−162.86 (17)	O3—C6—C7—C8	179.11 (17)
C5—O1—C2—O2	−176.8 (2)	O4—C6—C7—C8	60.8 (2)
C5—O1—C2—C3	3.2 (2)	O5—C7—C8—O6	68.0 (2)
O2—C2—C3—C4	176.8 (3)	C6—C7—C8—O6	−172.30 (16)
O1—C2—C3—C4	−3.3 (3)	O5—C7—C8—C9	−171.50 (16)
C2—C3—C4—C5	2.0 (3)	C6—C7—C8—C9	−51.8 (2)
C2—O1—C5—C4	−2.0 (2)	O6—C8—C9—O7	−71.42 (19)
C2—O1—C5—C1	120.06 (19)	C7—C8—C9—O7	168.07 (16)
C3—C4—C5—O1	−0.1 (3)	O6—C8—C9—C10	169.60 (14)
C3—C4—C5—C1	−116.2 (2)	C7—C8—C9—C10	49.1 (2)
O3—C1—C5—O1	−175.41 (16)	C6—O4—C10—C11	−177.97 (16)
O3—C1—C5—C4	−60.8 (2)	C6—O4—C10—C9	62.1 (2)
C1—O3—C6—O4	−61.2 (2)	O7—C9—C10—O4	−169.84 (18)
C1—O3—C6—C7	179.26 (17)	C8—C9—C10—O4	−51.1 (2)
C10—O4—C6—O3	171.64 (15)	O7—C9—C10—C11	72.0 (2)
C10—O4—C6—C7	−69.02 (19)	C8—C9—C10—C11	−169.25 (17)
O3—C6—C7—O5	−64.4 (2)	O4—C10—C11—O8	74.2 (2)
O4—C6—C7—O5	177.31 (17)	C9—C10—C11—O8	−167.27 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5O···O8^i	0.86 (3)	2.17 (3)	2.910 (2)	144 (3)
O6—H6O···O5^ii	0.92 (3)	1.94 (3)	2.824 (2)	162 (3)
O7—H7O···O6^ii	0.84 (3)	1.84 (3)	2.668 (2)	173 (3)
O8—H8O···O2^iii	0.88 (3)	1.96 (3)	2.830 (2)	167 (3)
C3—H3···O4^iv	0.95	2.55	3.413 (3)	151
C4—H4···O1^v	0.95	2.57	3.504 (3)	168
C8—H8···O7^vi	1.00	2.37	3.306 (3)	155
C1—H1A···O2^iii	0.99	2.38	3.289 (3)	153
C10—H10···O6^vii	1.00	2.43	3.415 (3)	167
O6—H6O···O7	0.92 (3)	2.56 (3)	2.894 (2)	102 (2)
C11—H11A···O7	0.99	2.59	2.986 (3)	104

Symmetry codes: (i) x−1, y−1, z; (ii) −x, y+1/2, −z+1; (iii) −x+2, y+1/2, −z+2; (iv) −x+1, y−1/2, −z+2; (v) x−1, y, z; (vi) −x+1, y−1/2, −z+1; (vii) x+1, y, z.