2-Phenyl­ethyl 1-thio-β-d-galactopyran­oside hemihydrate

Iván Brito; László Szilágyi; Ambati Ashok Kumar; Joselyn Albanez; Michael Bolte

doi:10.1107/S1600536811031667

. 2011 Aug 11;67(Pt 9):o2308–o2309. doi: 10.1107/S1600536811031667

2-Phenylethyl 1-thio-β-d-galactopyranoside hemihydrate

Iván Brito ^a,^*, László Szilágyi ^b, Ambati Ashok Kumar ^b, Joselyn Albanez ^a, Michael Bolte ^c

PMCID: PMC3200876 PMID: 22058941

Abstract

The title compound, C₁₄H₂₀O₅S·0.5H₂O, crystallizes with two organic molecules and a solvent water molecule in the asymmetric unit. In both molecules, the hexapyranosyl rings adopt a slightly distorted chair conformation (⁵ C ₂) with four substituents in equatorial positions and one substituent in an axial position. The main difference between the organic molecules is the dihedral angle between the phenyl ring and the best plane defined by the O—C₁—C₂—C₃ atoms (r.m.s deviations = 0.003 and 0.043 Å) of the hexapyranosyl rings [47.4 (4) and 86.5 (4)°]. In the asymmetric unit, molecules are linked by two strong O—H⋯O hydrogen bonds. In the crystal, the components are linked by a total of 10 distinct O—H⋯O hydrogen bonds, resulting in the formation of a two-dimensional network parallel to the ab plane.

Related literature

For synthetic methods see: Helferich & Türk (1956 ▶). For pharmacological properties of the title compound, see: De Bruyne et al. (1977 ▶); Choi et al. (2003 ▶). Gutiérrez et al. (2011 ▶). For puckering parameters see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₄H₂₀O₅S·0.5H₂O
M _r = 309.37
Orthorhombic,
a = 4.8358 (4) Å
b = 14.8218 (16) Å
c = 41.390 (3) Å
V = 2966.6 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.24 mm⁻¹
T = 173 K
0.20 × 0.09 × 0.08 mm

Data collection

Stoe IPDS II two-circle diffractometer
Absorption correction: multi-scan (MULABS; Spek, 200; ▶ Blessing, 1995 ▶) T _min = 0.954, T _max = 0.981
14206 measured reflections
5217 independent reflections
2395 reflections with I > 2σ(I)
R _int = 0.169

Refinement

R[F ² > 2σ(F ²)] = 0.058
wR(F ²) = 0.117
S = 0.68
5217 reflections
377 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.30 e Å⁻³
Absolute structure: Flack (1983 ▶), 2269 Friedel pairs
Flack parameter: −0.25 (16)

Data collection: X-AREA (Stoe & Cie, 2001 ▶); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶)’.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811031667/om2454sup1.cif

e-67-o2308-sup1.cif^{(27.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811031667/om2454Isup2.hkl

e-67-o2308-Isup2.hkl^{(255.5KB, hkl)}

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
O31—H31⋯O1W	0.84	1.92	2.759 (7)	179
O41—H41⋯O41A	0.84	1.95	2.779 (7)	169
O51—H51⋯O1Wⁱ	0.84	1.98	2.773 (6)	156
O61—H61⋯O31Aⁱⁱ	0.84	1.86	2.697 (7)	172
O31A—H31A⋯O61ⁱⁱⁱ	0.84	1.92	2.650 (7)	145
O41A—H41A⋯O41^iv	0.84	2.05	2.788 (7)	147
O51A—H51A⋯O61A^v	0.84	2.10	2.785 (7)	138
O61A—H61A⋯O31ⁱⁱ	0.84	2.02	2.744 (6)	145
O1W—H1WA⋯O31^v	0.84	2.23	2.989 (8)	150
O1W—H1WB⋯O41A^v	0.84	2.43	3.270 (6)	180

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

Acknowledgments

We thank OTKA, the Hungarian Scientific Research Fund (grant Nos. IN-79731 and NK-68578) for financial support. IB thanks the Spanish Research Council (CSIC) for the provision of a free-of-charge license to the Cambridge Structural Database.

supplementary crystallographic information

Comment

2-Phenylethyl-1-thio-β-D-galactopyranoside is one of the most potent inhibitors of β-galactosidase (EC 3.2.1.23) (De Bruyne,et al., 1977) and a radiologically labeled derivative has also been used for imaging of LacZ gene expression. (Choi et al., 2003). It was recently found to be moderately active in tests against Trypanosoma cruzi, the causal agent of Chagas disease (Gutiérrez et al., 2011). In the title compound, it crystallizes with two organic molecules and a solvent water molecule in the asymmetric unit, Fig. 1. In both molecules the hexapyranosyl rings adopts a slightly distorted chair conformation (⁵C₂) (Q_T= 0.574 (6) Å, θ= 3.4 (6)°, φ₂ = 8(9)°; Q_T= 0.587 (6) Å, θ= 9.2 (7)°, φ₂ = 299 (4)° for both molecules respectively), (Cremer & Pople, 1975) with four substituents in equatorial positions and one substituent in an axial position. The main difference between the organic molecules is the dihedral angle between the phenyl ring and the best plane defined by the atoms O1/C2/C3/C4 and O1A/C2A/C3A/C4A (r.m.s deviation 0.003 Å; 0.043Å respectively), of the hexapyranosyl rings [47.4 (4) and 86.5 (4)°]. The max. deviation for the best planes of the hexapyranosyl rings are: 0.290 (7)Å and 0.050 (6) Å) for molecules A and B respectively. The mean bond distances are: C—O 1.425 (7) Å, Csp3—Csp3 1.524 (9)Å and aromatic C—C 1.386 (11) Å. In the asymmetric unit the three molecules are linked by two strong O— H···O hydrogen bonds and the crystal packing is stabilized by eight O— H···O hydrogen bonding leading to the formation of a two-dimensional network parallel to the ab plane, Fig. 2, Table 1.

Experimental

1-thio-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose(0.364 g,1 mmol) was dissolved in acetonitrile (2 ml) and 1-bromo-2-phenylethane (0.185 g, 1 mmol) and triethyl amine (242µl, 2 mmol) added. The reaction mixture was stirred at RT until disappearence of the starting materials (TLC, 60 min). The solvent was removed under reduced pressure, and the residue purified by column chromatography (EtOAc: hexane - 8: 2) to give 2-phenylethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (1). Syrup, 402 mg (86%). [α]_D -22.9(CHCl₃,c 0.15), Lit. (Helferich & Türk, 1956). [α]_D -19.2 (CHCl₃). HR—MS:m/z calcd. for C₂₂H₂₈O₉S[M+Na]⁺: 491.135. Found: 491.138. ¹H-NMR (CDCl₃, 500 MHz): δ 7.20–7.35 (m,5H, Phenyl-H); 5.44 (br.s, 1H, H-4); 5.26 (t, 1H, H-2, J_2,3 9.9 Hz); 5.03 (br.d, 1H, H-3); 4.44 (d, 1H, H-1, J_1,2 10.1 Hz); 4.10–4.20 (m,2H, H-6a,b); 3.90 (m, 1H, H-5); 2.92 (m, 1H, S-CH_2a); 2.94 (m, 2H, Ph-CH₂); 3.00 (m, 1H, S-CH_{2 b});2.16, 2.06, 2.04,1.99 (s, 4x3H, 4x COCH₃);¹³C-NMR (CDCl₃, 125 MHz): δ 130.5 (Phenyl-C); 85.6 (C-1); 76.5(C-5); 73.3 (C-3); 69.0 (C-4); 68.7 (C-2); 62.2 (C-6); 38.2 (Ph-CH₂); 33.1 (S-CH₂); 22.3 (4xCOCH₃). The product (0.300 g, 0.64 mmol) was deacetylated by treatment with catalytic amount of NaOMe in methanol. The reaction mixture was stirred at room temperature until completion (TLC 20 min). After neutralization with a cation exchanger (Amberlyst 15) the solvent was removed under reduced pressure and the title molecule, 2-phenylethyl- 1-thio-β-D-galactopyranoside, was isolated as a white solid (MeOH: EtOAc - 2:8), 185 mg (96.3%). [α]_D -22.4 (MeOH, c 0.11). Lit. (Helferich &Türk,1956) [α]_D -32.2 (MeOH). HR—MS: m/z calcd. for C₁₄H₂₀O₅S [M+Na]⁺:323.094. Found: 323.094.

¹H-NMR(CD₃OD, 500 MHz): δ 7.15–7.30 (m, 5H, Phenyl-H); 4.34 (d, 1H, H-1, J_1,2 9.6 Hz); 3.90 (dd, 1H,H-4, J_4,5 ~ 1 Hz); 3.77(dd, 1H, H-6a, J_{6a,6 b} 11.5 Hz, J_5,6a 6.6 Hz); 3.71(dd, 1H, H-6 b, J_{5,6 b} 5.3 Hz); 3.57 (t, 1H, H-2, J_2,3 9.6 Hz); 3.53(m, 1H, H-5); 3.46 (1H, dd, H-3, J_3,4 3.4 Hz);2.92 (m, 1H, S-CH_2a);2.95 (m, 2H, Ph-CH₂); 3.02(m, 1H, S-CH_{2 b}); ¹³C-NMR (CDCl₃, 125 MHz): δ 131.3, 131.0, 128.9 (Phenyl-C); 88.4 (C-1); 81.5 (C-5); 77.1 (C-3);72.3 (C-2); 71.3 (C-4); 63.5 (C-6); 38.6 (Ph-CH₂); 33.2 (S-CH₂). Colourless single crystals suitable for X-ray analysis were obtained by slow evaporation of an aqueous solution.