Ethyl α-d-sorboside monohydrate

Takashita, T.; Horii, Y.; Takeshita, K.; Ishii, T.

doi:10.1107/S2414314626008047

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 11| Part 8| August 2026| x260804

https://doi.org/10.1107/S2414314626008047

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Ethyl α-D-sorboside monohydrate

Tomoko Takashita,^a ^* Yoji Horii,^a Kei Takeshita ^b and Tomohiko Ishii ^a

^aGraduate School of Science for Creative Emergence, Kagawa University, 2217-20 Hayashi-cho, Takamatsu, Kagawa 761-0396, Japan, and ^bFUSHIMI Pharmaceutical Co., Ltd., 307 Minatomachi, Marugame, Kagawa 763-8605, Japan
^*Correspondence e-mail: [email protected]

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 3 August 2026; accepted 5 August 2026; online 7 August 2026)

The title compound, C₈H₁₆O₆·H₂O, was prepared by Fischer glycosylation of D-sorbose with ethanol. Colorless block-shaped single crystals suitable for single-crystal X-ray diffraction were obtained. The title compound crystallizes in the orthorhombic space group P2₁2₁2₁, with one sorboside molecule and one water molecule in the asymmetric unit. The sorboside molecule adopts an α-pyranose form with a ⁵C₂ chair conformation. In the crystal, the sorboside and water molecules are linked by O—H⋯O hydrogen bonds, forming an extended hydrogen-bonded network.

Keywords: crystal structure; hydrogen bonding; rare sugar; ethyl sorboside; monohydrate.

CCDC reference: 2577733

Structure description

Rare sugars are monosaccharides and their derivatives that occur only in limited quantities in nature (Izumori, 2002 ). D-Sorbose is a rare ketohexose, and its alkyl glycosides provide useful examples for examining how substitution at the anomeric centre affects molecular conformation, hydration and crystal packing. The title compound, ethyl α-D-sorboside monohydrate, is an ethyl glycoside of D-sorbose in which the anomeric hydroxy group at C2 is replaced by an ethoxy group. In the present study, its single-crystal structure was determined and compared with the previously reported anhydrous structure of ethyl α-L-sorboside (Nagayama et al., 2020 ).

The title compound crystallizes in the orthorhombic space group P2₁2₁2₁. The asymmetric unit contains one ethyl α-D-sorboside molecule and one water molecule. The sorboside molecule adopts an α-pyranose form with a ⁵C₂ chair conformation and the ethoxy substituent at the anomeric C2 atom occupying an axial position (Fig. 1). The stereogenic centres C2, C3, C4 and C5 have S, R, S and R configurations, respectively. The C2—O2—C7—C8 torsion angle is −173.8 (2)°.

Figure 1
The molecular structure of the asymmetric unit of the title compound, showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radius. The O4—H4⋯O7 hydrogen bond between the sorboside and water molecules is shown as a dashed line.

The anhydrous crystal structure of ethyl α-L-sorboside (CSD refcode EJAKAE; Nagayama et al., 2020) also belongs to space group P2₁2₁2₁, with a unit-cell volume of 940.63 (19) Å³ and Z = 4. The unit-cell volume of the present monohydrate is therefore 151.35 Å³ (16.1%) larger. This difference is consistent with the inclusion of four water molecules of crystallization per unit cell, together with the resulting change in crystal packing. After inversion of the L-sorboside molecule, least-squares fitting of all 14 non-hydrogen atoms to the corresponding atoms of the present D-sorboside molecule gave an r.m.s. deviation of 0.441 Å The principal conformational difference is the orientation of the hydroxymethyl group at C1, as indicated by the O1—C1—C2—C3 torsion angles of −1257.1 (3)° in the title monohydrate and −153.2 (2)° in the inverted EJAKAE molecule. By contrast, the sorbopyranose ring conformations and the anti conformations of the ethoxy groups are closely similar.

In the crystal, the sorboside and water molecules are connected by the O1—H1⋯O3, O1—H1⋯O4, O3—H3⋯O4, O4—H4⋯O7, O5—H5⋯O3, O7—H7C⋯O5 and O7—H7D⋯O1 hydrogen bonds listed in Table 1. The O1—H1 group participates in a bifurcated hydrogen bond, with the O3 and O4 atoms acting as acceptors. The donor⋯acceptor distances range from 2.618 (3) to 3.018 (2) Å. Taken together, the seven O—H⋯O hydrogen bonds generate a two-dimensional hydrogen-bonded network extending parallel to the (001) plane. The crystal packing and all seven hydrogen bonds listed in Table 1 are shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O3ⁱ	0.82	2.36	3.018 (2)	137
O1—H1⋯O4ⁱ	0.82	2.25	2.975 (3)	148
O3—H3⋯O4ⁱ	0.82	1.93	2.741 (2)	167
O4—H4⋯O7	0.82	1.82	2.618 (3)	165
O5—H5⋯O3ⁱⁱ	0.82	2.08	2.842 (3)	154
O7—H7C⋯O5ⁱⁱⁱ	0.85	1.90	2.738 (3)	168
O7—H7D⋯O1^iv	0.85	2.09	2.909 (3)	163
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) ; (iii) $[-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iv) $[-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
A portion of the crystal packing of the title compound, shown in an oblique view with the unit-cell directions indicated. The central sorboside molecule and the water molecule are shown using a ball-and-stick representation, whereas the surrounding sorboside molecules are shown using a capped-stick representation. The seven crystallographically distinct O—H⋯O hydrogen bonds listed in Table 1

are shown as cyan dashed lines.

Synthesis and crystallization

Ethyl α-D-sorboside monohydrate was prepared by Fischer glycosylation of D-sorbose with ethanol. Because the reaction produced a mixture of isomeric products, including α- and β-anomers and furanose forms, the reaction mixture was separated by ion-exchange chromatography. Fractions containing the desired product were combined and concentrated to give a syrup, which was allowed to stand at room temperature. Colorless block-shaped single crystals suitable for single-crystal X-ray diffraction were obtained. The absolute configuration was assigned on the basis of the known configuration of the D-sorbose starting material and the synthetic route.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The Flack parameter supports the absolute configuration expected from the use of D-sorbose as the starting material.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₁₆O₆·H₂O
M_r	226.22
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	296
a, b, c (Å)	6.6457 (2), 7.5616 (2), 21.7300 (6)
V (Å³)	1091.98 (5)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	1.05
Crystal size (mm)	0.1 × 0.1 × 0.1

Data collection
Diffractometer	Rigaku R-AXIS RAPID
Absorption correction	Multi-scan (ABSCOR; Rigaku, 1995 )
T_min, T_max	0.702, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	12255, 1969, 1706
R_int	0.054
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.031, 0.076, 1.02
No. of reflections	1969
No. of parameters	144
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.15, −0.13
Absolute structure	Flack x determined using 626 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.04 (11)
Computer programs: RAPID-AUTO (Rigaku, 2009 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2577733

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314626008047/vm4080sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314626008047/vm4080Isup3.hkl

Point-by-point response to the Co-editors comments, detailing the revisions made to the manuscript, Table 2, and Figures 1 and 2 (manuscript vm4080). DOI: https://doi.org/10.1107/S2414314626008047/vm4080sup3.docx

checkCIF report

Computing details top

Ethyl α-D-sorboside monohydrate top

Crystal data top

C₈H₁₆O₆·H₂O	D_x = 1.376 Mg m⁻³
M_r = 226.22	Cu Kα radiation, λ = 1.5418 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 11105 reflections
a = 6.6457 (2) Å	θ = 4.1–68.1°
b = 7.5616 (2) Å	µ = 1.05 mm⁻¹
c = 21.7300 (6) Å	T = 296 K
V = 1091.98 (5) Å³	Block, clear light colourless
Z = 4	0.1 × 0.1 × 0.1 mm
F(000) = 488

Data collection top

Rigaku R-AXIS RAPID diffractometer	1706 reflections with I > 2σ(I)
ω scans	R_int = 0.054
Absorption correction: multi-scan (ABSCOR; Rigaku, 1995)	θ_max = 68.1°, θ_min = 4.1°
T_min = 0.702, T_max = 1.000	h = −7→7
12255 measured reflections	k = −9→9
1969 independent reflections	l = −26→25

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.031	w = 1/[σ²(F_o²) + (0.0327P)² + 0.1352P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.076	(Δ/σ)_max < 0.001
S = 1.02	Δρ_max = 0.15 e Å⁻³
1969 reflections	Δρ_min = −0.13 e Å⁻³
144 parameters	Absolute structure: Flack x determined using 626 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: −0.04 (11)
Primary atom site location: dual

Special details top

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

Refinement. The structure was solved using SHELXT (Sheldrick, 2015a) and refined against F² by full-matrix least-squares methods using SHELXL (Sheldrick, 2015b). All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were placed in calculated positions and refined using constrained models. The final refinement gave R₁ = 0.0311 for reflections with I > 2σ(I) and wR₂ = 0.0759 for all data. The maximum and minimum residual electron densities were 0.15 and -0.13 e Å^-3, respectively.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.5536 (3)	0.9834 (2)	0.34665 (8)	0.0487 (5)
H1	0.502283	0.981931	0.312334	0.073*
O2	0.4803 (2)	0.5405 (2)	0.41294 (7)	0.0409 (4)
O3	0.4025 (2)	0.5562 (2)	0.28922 (7)	0.0392 (4)
H3	0.348364	0.643371	0.274062	0.059*
O4	0.7416 (3)	0.3772 (2)	0.24941 (7)	0.0443 (5)
H4	0.840422	0.417639	0.231721	0.066*
O5	1.0724 (3)	0.3576 (2)	0.33542 (10)	0.0572 (5)
H5	1.187162	0.394017	0.329875	0.086*
O6	0.7715 (3)	0.7138 (2)	0.40269 (7)	0.0409 (4)
C1	0.4643 (4)	0.8509 (3)	0.38368 (11)	0.0418 (6)
H1A	0.326162	0.833089	0.370681	0.050*
H1B	0.462452	0.890214	0.426162	0.050*
C2	0.5773 (4)	0.6760 (3)	0.37952 (10)	0.0350 (5)
C3	0.5945 (3)	0.6048 (3)	0.31342 (10)	0.0314 (5)
H3A	0.651070	0.698141	0.287380	0.038*
C4	0.7331 (4)	0.4455 (3)	0.31061 (10)	0.0350 (5)
H4A	0.679010	0.353462	0.337700	0.042*
C5	0.9361 (4)	0.5024 (3)	0.33518 (11)	0.0390 (6)
H5A	0.990207	0.597101	0.309203	0.047*
C6	0.9110 (4)	0.5700 (4)	0.40010 (11)	0.0455 (6)
H6A	0.863529	0.474734	0.426218	0.055*
H6B	1.040394	0.608870	0.415706	0.055*
C7	0.4558 (5)	0.5640 (4)	0.47787 (11)	0.0590 (8)
H7A	0.365283	0.661921	0.485898	0.071*
H7B	0.584626	0.590126	0.496772	0.071*
C8	0.3727 (6)	0.4001 (5)	0.50366 (15)	0.0775 (11)
H8A	0.243423	0.377111	0.485613	0.116*
H8B	0.358345	0.412393	0.547409	0.116*
H8C	0.461880	0.303491	0.494816	0.116*
O7	1.0151 (3)	0.5050 (3)	0.17499 (12)	0.0711 (7)
H7C	1.005187	0.615896	0.169385	0.107*
H7D	1.134246	0.479972	0.163735	0.107*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0558 (12)	0.0388 (10)	0.0513 (11)	−0.0007 (9)	−0.0042 (9)	0.0038 (8)
O2	0.0448 (10)	0.0422 (9)	0.0355 (8)	−0.0050 (8)	0.0050 (7)	0.0031 (8)
O3	0.0291 (9)	0.0433 (10)	0.0452 (10)	0.0004 (9)	−0.0072 (7)	−0.0025 (8)
O4	0.0376 (10)	0.0476 (10)	0.0477 (10)	−0.0057 (9)	0.0075 (8)	−0.0148 (8)
O5	0.0296 (10)	0.0428 (10)	0.0992 (15)	0.0029 (9)	0.0004 (10)	−0.0055 (10)
O6	0.0369 (9)	0.0417 (10)	0.0440 (9)	−0.0032 (8)	−0.0075 (8)	−0.0067 (7)
C1	0.0453 (15)	0.0396 (14)	0.0405 (13)	0.0025 (12)	0.0016 (11)	−0.0047 (11)
C2	0.0331 (13)	0.0361 (13)	0.0359 (12)	−0.0046 (11)	−0.0009 (11)	−0.0009 (10)
C3	0.0276 (12)	0.0334 (12)	0.0332 (11)	−0.0029 (11)	0.0009 (9)	−0.0002 (9)
C4	0.0311 (12)	0.0350 (13)	0.0389 (13)	−0.0015 (12)	0.0031 (10)	−0.0042 (11)
C5	0.0275 (13)	0.0353 (14)	0.0543 (14)	−0.0002 (10)	0.0006 (11)	−0.0022 (11)
C6	0.0329 (13)	0.0487 (15)	0.0549 (15)	0.0018 (13)	−0.0119 (11)	−0.0002 (13)
C7	0.070 (2)	0.072 (2)	0.0348 (13)	−0.0081 (19)	0.0069 (13)	0.0024 (14)
C8	0.091 (3)	0.082 (2)	0.060 (2)	0.002 (2)	0.0174 (18)	0.0237 (18)
O7	0.0619 (14)	0.0485 (13)	0.1028 (17)	0.0016 (10)	0.0380 (12)	0.0090 (11)

Geometric parameters (Å, º) top

O1—H1	0.8200	C3—H3A	0.9800
O1—C1	1.415 (3)	C3—C4	1.517 (3)
O2—C2	1.412 (3)	C4—H4A	0.9800
O2—C7	1.431 (3)	C4—C5	1.514 (3)
O3—H3	0.8200	C5—H5A	0.9800
O3—C3	1.428 (3)	C5—C6	1.510 (3)
O4—H4	0.8200	C6—H6A	0.9700
O4—C4	1.428 (3)	C6—H6B	0.9700
O5—H5	0.8200	C7—H7A	0.9700
O5—C5	1.421 (3)	C7—H7B	0.9700
O6—C2	1.414 (3)	C7—C8	1.468 (4)
O6—C6	1.430 (3)	C8—H8A	0.9600
C1—H1A	0.9700	C8—H8B	0.9600
C1—H1B	0.9700	C8—H8C	0.9600
C1—C2	1.524 (3)	O7—H7C	0.8501
C2—C3	1.538 (3)	O7—H7D	0.8498

C1—O1—H1	109.5	C5—C4—C3	107.55 (19)
C2—O2—C7	118.0 (2)	C5—C4—H4A	108.5
C3—O3—H3	109.5	O5—C5—C4	110.50 (18)
C4—O4—H4	109.5	O5—C5—H5A	109.4
C5—O5—H5	109.5	O5—C5—C6	109.2 (2)
C2—O6—C6	115.07 (18)	C4—C5—H5A	109.4
O1—C1—H1A	109.2	C6—C5—C4	109.10 (19)
O1—C1—H1B	109.2	C6—C5—H5A	109.4
O1—C1—C2	112.0 (2)	O6—C6—C5	111.47 (19)
H1A—C1—H1B	107.9	O6—C6—H6A	109.3
C2—C1—H1A	109.2	O6—C6—H6B	109.3
C2—C1—H1B	109.2	C5—C6—H6A	109.3
O2—C2—O6	112.37 (18)	C5—C6—H6B	109.3
O2—C2—C1	111.97 (18)	H6A—C6—H6B	108.0
O2—C2—C3	105.08 (18)	O2—C7—H7A	110.0
O6—C2—C1	104.65 (19)	O2—C7—H7B	110.0
O6—C2—C3	109.62 (19)	O2—C7—C8	108.3 (3)
C1—C2—C3	113.31 (19)	H7A—C7—H7B	108.4
O3—C3—C2	111.58 (18)	C8—C7—H7A	110.0
O3—C3—H3A	108.4	C8—C7—H7B	110.0
O3—C3—C4	108.88 (18)	C7—C8—H8A	109.5
C2—C3—H3A	108.4	C7—C8—H8B	109.5
C4—C3—C2	111.12 (18)	C7—C8—H8C	109.5
C4—C3—H3A	108.4	H8A—C8—H8B	109.5
O4—C4—C3	110.43 (18)	H8A—C8—H8C	109.5
O4—C4—H4A	108.5	H8B—C8—H8C	109.5
O4—C4—C5	113.33 (19)	H7C—O7—H7D	104.5
C3—C4—H4A	108.5

O1—C1—C2—O2	−175.77 (18)	C2—O2—C7—C8	−173.8 (2)
O1—C1—C2—O6	62.2 (2)	C2—O6—C6—C5	57.3 (3)
O1—C1—C2—C3	−57.1 (3)	C2—C3—C4—O4	177.90 (18)
O2—C2—C3—O3	56.1 (2)	C2—C3—C4—C5	−58.0 (2)
O2—C2—C3—C4	−65.6 (2)	C3—C4—C5—O5	178.40 (18)
O3—C3—C4—O4	54.6 (2)	C3—C4—C5—C6	58.4 (2)
O3—C3—C4—C5	178.73 (18)	C4—C5—C6—O6	−57.9 (3)
O4—C4—C5—O5	−59.3 (3)	C6—O6—C2—O2	61.8 (2)
O4—C4—C5—C6	−179.3 (2)	C6—O6—C2—C1	−176.52 (19)
O5—C5—C6—O6	−178.70 (19)	C6—O6—C2—C3	−54.7 (2)
O6—C2—C3—O3	177.04 (18)	C7—O2—C2—O6	56.5 (3)
O6—C2—C3—C4	55.3 (2)	C7—O2—C2—C1	−61.0 (3)
C1—C2—C3—O3	−66.5 (2)	C7—O2—C2—C3	175.6 (2)
C1—C2—C3—C4	171.8 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O3ⁱ	0.82	2.36	3.018 (2)	137
O1—H1···O4ⁱ	0.82	2.25	2.975 (3)	148
O3—H3···O4ⁱ	0.82	1.93	2.741 (2)	167
O4—H4···O7	0.82	1.82	2.618 (3)	165
O5—H5···O3ⁱⁱ	0.82	2.08	2.842 (3)	154
O7—H7C···O5ⁱⁱⁱ	0.85	1.90	2.738 (3)	168
O7—H7D···O1^iv	0.85	2.09	2.909 (3)	163

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

Acknowledgements

The authors gratefully acknowledge Professor Genta Sakane (Okayama University of Science) for insightful discussions and valuable technical guidance. Support from the JST Support for Pioneering Research Initiated by the Next Generation (SPRING) program is also sincerely acknowledged.

References

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Izumori, K. (2002). Naturwissenschaften 89, 120–124. CrossRef PubMed CAS Google Scholar
Nagayama, N., Taniguchi, N., Matsumoto, M., Takeshita, K. & Ishii, T. (2020). IUCrData 5, x201625. Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Rigaku (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan. Google Scholar
Rigaku (2009). RAPID-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar

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