Methyl β-L-lactoside, C13H24O11, (II), is described by glycosidic torsion angles φ (O5Gal—C1Gal—O4Glc—C4Glc) and ψ (C1Gal—O1Gal—C4Glc—C5Glc) of 93.89 (13) and −127.43 (13)°, respectively, where the ring atom numbering conforms to the convention in which C1 is the anomeric C atom and C6 is the exocyclic hydroxymethyl (CH2OH) C atom in both residues (Gal is galactose and Glc is glucose). Substitution of L-Gal for D-Gal in the biologically relevant disaccharide, methyl β-lactoside [Stenutz, Shang & Serianni (1999). Acta Cryst. C55, 1719–1721], (I), significantly alters the glycosidic linkage interface. In the crystal structure of (I), one inter-residue (intramolecular) hydrogen bond is observed between atoms H3OGlc and O5Gal. In contrast, in the crystal structure of (II), inter-residue hydrogen bonds are observed between atoms H6OGlc and O5Gal, H6OGlc and O6Gal, and H3OGlc and O2Gal, with H6OGlc serving as a donor with two intramolecular acceptors.
Supporting information
CCDC reference: 299638
Compound (II) was prepared by coupling 2,3,4,6-tetra-O-acetyl-α-L-galactopyranosyl trichloroacetimidate, (IV) (600 mg, 1.21 mmol), with methyl 2,3,6-tri-O-benzyl-β-D-glucopyranoside, (V) (500 mg, 1.08 mmol), in the presence of silver trifluoromethanesulfonate (350 mg, 1.4 mmol) in dichloromethane (20 ml) at 253 K. When the reaction was complete (2 h), the product was deprotected at room temperature with 400 mg of 10% Pd/C in 20 ml EtOAc, followed by 15 ml of a 0.1 M methanol solution of NaOCH3. Compound (IV) was prepared by standard methods (Schmidt et al., 1984) and (V) was prepared by reacting methyl 2,3-di-O-benzyl-4,6-O-benzylidene-β-D-glucopyranoside (450 mg, 0.97 mmol) in tetrahydrofuran (30 ml) with NaBH3CN (0.85 g, 13.7 mmol), immediately followed by the addition of 1 N HCl in Et2O (14 ml). Purification of (II) was achieved by chromatography on silica gel using methanol/dichloromethane (1:4) as the solvent. Crystals were grown from a methanol solution by slow evaporation at 277 K.
Hydroxy H atoms were located in a difference electron density map and freely refined in subsequent cycles of least-squares refinement, including an isotropic displacement parameter. All other H atoms were placed at calculated positions and allowed to ride on the parent atom. Displacement parameters for these H atoms were set to 1.2 times Ueq of the parent atom (1.5 times for methyl H atoms). 2143 Friedel pairs were merged in the final stages of refinement, and the Flack parameter is thus meaningless. The absolute configuration was assumed from the synthesis.
Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 and SAINT (Bruker, 2004); data reduction: SAINT and XPREP (Sheldrick, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Sheldrick, 1998); software used to prepare material for publication: XCIF (Sheldrick, 2001) and enCIFer (Allen et al., 2004).
Methyl 4-O-
β-
L-galactopyranosyl-
β-
D-glucopyranoside
top
Crystal data top
C13H24O11 | F(000) = 760 |
Mr = 356.32 | Dx = 1.529 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 4991 reflections |
a = 4.7087 (4) Å | θ = 2.9–31.3° |
b = 14.1428 (12) Å | µ = 0.14 mm−1 |
c = 23.2401 (19) Å | T = 100 K |
V = 1547.7 (2) Å3 | Needle, colorless |
Z = 4 | 0.35 × 0.07 × 0.05 mm |
Data collection top
Bruker X8-APEX-II CCD diffractometer | 2644 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.031 |
Graphite monochromator | θmax = 31.5°, θmin = 1.7° |
Detector resolution: 8.33 pixels mm-1 | h = −6→4 |
ϕ and ω scans | k = −16→20 |
13853 measured reflections | l = −30→34 |
2964 independent reflections | |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.033 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.088 | w = 1/[σ2(Fo2) + (0.0559P)2 + 0.1003P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.002 |
2964 reflections | Δρmax = 0.45 e Å−3 |
246 parameters | Δρmin = −0.21 e Å−3 |
0 restraints | Absolute structure: Flack (1983), 2143 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.5 (7) |
Crystal data top
C13H24O11 | V = 1547.7 (2) Å3 |
Mr = 356.32 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 4.7087 (4) Å | µ = 0.14 mm−1 |
b = 14.1428 (12) Å | T = 100 K |
c = 23.2401 (19) Å | 0.35 × 0.07 × 0.05 mm |
Data collection top
Bruker X8-APEX-II CCD diffractometer | 2644 reflections with I > 2σ(I) |
13853 measured reflections | Rint = 0.031 |
2964 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.033 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.088 | Δρmax = 0.45 e Å−3 |
S = 1.04 | Δρmin = −0.21 e Å−3 |
2964 reflections | Absolute structure: Flack (1983), 2143 Friedel pairs |
246 parameters | Absolute structure parameter: 0.5 (7) |
0 restraints | |
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. |
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 (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.9108 (3) | 0.66870 (10) | 0.14464 (6) | 0.0096 (3) | |
H1 | 0.7218 | 0.6674 | 0.1250 | 0.012* | |
C2 | 0.9964 (3) | 0.77062 (10) | 0.15776 (6) | 0.0098 (3) | |
H2 | 1.1952 | 0.7717 | 0.1729 | 0.012* | |
C3 | 0.7967 (3) | 0.81224 (10) | 0.20249 (6) | 0.0093 (3) | |
H3 | 0.6025 | 0.8168 | 0.1853 | 0.011* | |
C4 | 0.7811 (3) | 0.74872 (11) | 0.25573 (6) | 0.0102 (3) | |
H4 | 0.6351 | 0.7740 | 0.2829 | 0.012* | |
C5 | 0.6967 (3) | 0.64917 (10) | 0.23670 (6) | 0.0100 (3) | |
H5 | 0.5060 | 0.6518 | 0.2178 | 0.012* | |
C6 | 0.6845 (4) | 0.58009 (10) | 0.28652 (7) | 0.0127 (3) | |
H6A | 0.8718 | 0.5771 | 0.3058 | 0.015* | |
H6B | 0.5421 | 0.6015 | 0.3150 | 0.015* | |
O1 | 1.1178 (2) | 0.62829 (8) | 0.10915 (4) | 0.0110 (2) | |
O2 | 0.9830 (3) | 0.82412 (8) | 0.10555 (5) | 0.0139 (2) | |
H2O | 1.136 (6) | 0.8529 (17) | 0.1016 (10) | 0.032 (7)* | |
O3 | 0.8901 (3) | 0.90494 (8) | 0.21699 (5) | 0.0137 (2) | |
H3O | 0.765 (6) | 0.9350 (17) | 0.2228 (10) | 0.022 (6)* | |
O4 | 1.0496 (2) | 0.74434 (8) | 0.28404 (5) | 0.0127 (2) | |
H4O | 1.082 (6) | 0.7944 (17) | 0.3007 (11) | 0.032 (7)* | |
O5 | 0.9017 (2) | 0.61307 (7) | 0.19595 (4) | 0.0103 (2) | |
O6 | 0.6083 (3) | 0.48807 (8) | 0.26504 (5) | 0.0136 (2) | |
H6O | 0.737 (6) | 0.4553 (18) | 0.2734 (11) | 0.035 (7)* | |
C1' | 1.1010 (3) | 0.43818 (11) | −0.02791 (6) | 0.0115 (3) | |
H1' | 1.3093 | 0.4468 | −0.0343 | 0.014* | |
C2' | 0.9456 (3) | 0.53228 (11) | −0.03710 (6) | 0.0107 (3) | |
H2' | 0.7383 | 0.5204 | −0.0311 | 0.013* | |
C3' | 1.0400 (3) | 0.60340 (10) | 0.00812 (6) | 0.0101 (3) | |
H3' | 1.2433 | 0.6204 | 0.0012 | 0.012* | |
C4' | 1.0104 (3) | 0.56104 (10) | 0.06809 (6) | 0.0094 (3) | |
H4' | 0.8049 | 0.5493 | 0.0762 | 0.011* | |
C5' | 1.1712 (3) | 0.46766 (10) | 0.07193 (6) | 0.0109 (3) | |
H5' | 1.3755 | 0.4789 | 0.0624 | 0.013* | |
C6' | 1.1519 (4) | 0.42083 (12) | 0.13065 (6) | 0.0135 (3) | |
H6'1 | 1.2348 | 0.3566 | 0.1282 | 0.016* | |
H6'2 | 1.2667 | 0.4576 | 0.1584 | 0.016* | |
C7' | 1.1687 (4) | 0.28773 (12) | −0.06836 (8) | 0.0225 (4) | |
H7'1 | 1.3671 | 0.3057 | −0.0749 | 0.034* | |
H7'2 | 1.1036 | 0.2474 | −0.1000 | 0.034* | |
H7'3 | 1.1533 | 0.2531 | −0.0320 | 0.034* | |
O1' | 0.9953 (3) | 0.37154 (8) | −0.06577 (5) | 0.0157 (2) | |
O2' | 0.9802 (3) | 0.56846 (8) | −0.09390 (5) | 0.0134 (2) | |
H2'O | 1.134 (7) | 0.592 (2) | −0.0977 (11) | 0.041 (8)* | |
O3' | 0.8692 (3) | 0.68598 (8) | 0.00254 (5) | 0.0152 (2) | |
H3'O | 0.939 (6) | 0.7267 (18) | 0.0205 (10) | 0.035 (7)* | |
O5' | 1.0503 (3) | 0.40568 (8) | 0.02969 (5) | 0.0122 (2) | |
O6' | 0.8663 (3) | 0.41363 (8) | 0.15189 (5) | 0.0144 (2) | |
H6'O | 0.851 (6) | 0.4572 (19) | 0.1705 (10) | 0.038 (8)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0095 (6) | 0.0097 (6) | 0.0096 (6) | −0.0001 (5) | 0.0005 (5) | 0.0005 (5) |
C2 | 0.0110 (6) | 0.0083 (6) | 0.0100 (6) | −0.0008 (5) | −0.0007 (5) | 0.0023 (5) |
C3 | 0.0091 (6) | 0.0063 (6) | 0.0125 (6) | 0.0002 (5) | −0.0001 (5) | 0.0008 (5) |
C4 | 0.0104 (6) | 0.0092 (6) | 0.0110 (6) | 0.0007 (5) | 0.0002 (5) | −0.0011 (5) |
C5 | 0.0100 (6) | 0.0095 (6) | 0.0106 (6) | −0.0004 (5) | 0.0020 (5) | 0.0006 (5) |
C6 | 0.0164 (7) | 0.0095 (6) | 0.0122 (6) | −0.0002 (5) | 0.0017 (6) | 0.0010 (5) |
O1 | 0.0107 (5) | 0.0122 (5) | 0.0099 (4) | −0.0009 (4) | 0.0007 (4) | −0.0038 (4) |
O2 | 0.0148 (5) | 0.0138 (5) | 0.0132 (5) | −0.0008 (4) | 0.0015 (4) | 0.0058 (4) |
O3 | 0.0111 (5) | 0.0067 (5) | 0.0232 (6) | 0.0007 (4) | 0.0000 (5) | −0.0022 (4) |
O4 | 0.0141 (5) | 0.0112 (5) | 0.0128 (5) | 0.0010 (4) | −0.0046 (4) | −0.0023 (4) |
O5 | 0.0133 (5) | 0.0087 (5) | 0.0090 (4) | 0.0009 (4) | 0.0025 (4) | 0.0004 (4) |
O6 | 0.0137 (5) | 0.0081 (5) | 0.0190 (6) | −0.0005 (4) | −0.0004 (5) | 0.0019 (4) |
C1' | 0.0138 (6) | 0.0106 (6) | 0.0102 (6) | −0.0006 (5) | −0.0002 (5) | −0.0006 (5) |
C2' | 0.0121 (7) | 0.0106 (6) | 0.0095 (6) | −0.0010 (5) | −0.0003 (5) | 0.0011 (5) |
C3' | 0.0128 (7) | 0.0078 (6) | 0.0097 (6) | 0.0009 (5) | −0.0012 (5) | 0.0007 (5) |
C4' | 0.0099 (6) | 0.0097 (6) | 0.0085 (6) | −0.0012 (5) | −0.0006 (5) | −0.0004 (5) |
C5' | 0.0131 (7) | 0.0095 (6) | 0.0100 (6) | −0.0002 (5) | −0.0003 (5) | 0.0009 (5) |
C6' | 0.0149 (7) | 0.0146 (7) | 0.0109 (6) | 0.0017 (6) | −0.0013 (6) | 0.0034 (5) |
C7' | 0.0277 (9) | 0.0139 (8) | 0.0258 (9) | 0.0036 (7) | 0.0007 (8) | −0.0077 (7) |
O1' | 0.0210 (6) | 0.0109 (5) | 0.0150 (5) | −0.0012 (5) | −0.0030 (5) | −0.0037 (4) |
O2' | 0.0163 (5) | 0.0147 (5) | 0.0093 (5) | −0.0016 (5) | −0.0007 (4) | 0.0026 (4) |
O3' | 0.0198 (6) | 0.0094 (5) | 0.0163 (5) | 0.0049 (4) | −0.0050 (5) | −0.0014 (4) |
O5' | 0.0170 (5) | 0.0097 (5) | 0.0099 (4) | −0.0016 (4) | −0.0014 (4) | 0.0006 (4) |
O6' | 0.0184 (6) | 0.0116 (5) | 0.0133 (5) | −0.0009 (4) | 0.0029 (5) | 0.0005 (4) |
Geometric parameters (Å, º) top
C1—O1 | 1.3988 (18) | C1'—O5' | 1.4352 (18) |
C1—O5 | 1.4293 (17) | C1'—C2' | 1.534 (2) |
C1—C2 | 1.528 (2) | C1'—H1' | 1.0000 |
C1—H1 | 1.0000 | C2'—O2' | 1.4252 (17) |
C2—O2 | 1.4313 (17) | C2'—C3' | 1.521 (2) |
C2—C3 | 1.521 (2) | C2'—H2' | 1.0000 |
C2—H2 | 1.0000 | C3'—O3' | 1.4240 (18) |
C3—O3 | 1.4234 (18) | C3'—C4' | 1.5235 (19) |
C3—C4 | 1.531 (2) | C3'—H3' | 1.0000 |
C3—H3 | 1.0000 | C4'—C5' | 1.525 (2) |
C4—O4 | 1.4268 (18) | C4'—H4' | 1.0000 |
C4—C5 | 1.528 (2) | C5'—O5' | 1.4338 (18) |
C4—H4 | 1.0000 | C5'—C6' | 1.519 (2) |
C5—O5 | 1.4455 (18) | C5'—H5' | 1.0000 |
C5—C6 | 1.516 (2) | C6'—O6' | 1.436 (2) |
C5—H5 | 1.0000 | C6'—H6'1 | 0.9900 |
C6—O6 | 1.4392 (18) | C6'—H6'2 | 0.9900 |
C6—H6A | 0.9900 | C7'—O1' | 1.441 (2) |
C6—H6B | 0.9900 | C7'—H7'1 | 0.9800 |
O1—C4' | 1.4390 (17) | C7'—H7'2 | 0.9800 |
O2—H2O | 0.83 (3) | C7'—H7'3 | 0.9800 |
O3—H3O | 0.74 (3) | O2'—H2'O | 0.80 (3) |
O4—H4O | 0.82 (2) | O3'—H3'O | 0.78 (3) |
O6—H6O | 0.79 (3) | O6'—H6'O | 0.76 (3) |
C1'—O1' | 1.3821 (18) | | |
| | | |
O1—C1—O5 | 106.72 (11) | O1'—C1'—H1' | 110.0 |
O1—C1—C2 | 108.61 (12) | O5'—C1'—H1' | 110.0 |
O5—C1—C2 | 111.15 (11) | C2'—C1'—H1' | 110.0 |
O1—C1—H1 | 110.1 | O2'—C2'—C3' | 111.66 (12) |
O5—C1—H1 | 110.1 | O2'—C2'—C1' | 112.70 (12) |
C2—C1—H1 | 110.1 | C3'—C2'—C1' | 109.77 (12) |
O2—C2—C3 | 110.33 (12) | O2'—C2'—H2' | 107.5 |
O2—C2—C1 | 108.54 (12) | C3'—C2'—H2' | 107.5 |
C3—C2—C1 | 109.78 (12) | C1'—C2'—H2' | 107.5 |
O2—C2—H2 | 109.4 | O3'—C3'—C2' | 108.32 (12) |
C3—C2—H2 | 109.4 | O3'—C3'—C4' | 110.75 (12) |
C1—C2—H2 | 109.4 | C2'—C3'—C4' | 110.20 (12) |
O3—C3—C2 | 109.10 (12) | O3'—C3'—H3' | 109.2 |
O3—C3—C4 | 111.34 (12) | C2'—C3'—H3' | 109.2 |
C2—C3—C4 | 110.80 (11) | C4'—C3'—H3' | 109.2 |
O3—C3—H3 | 108.5 | O1—C4'—C3' | 108.34 (11) |
C2—C3—H3 | 108.5 | O1—C4'—C5' | 111.06 (12) |
C4—C3—H3 | 108.5 | C3'—C4'—C5' | 110.42 (12) |
O4—C4—C5 | 108.90 (12) | O1—C4'—H4' | 109.0 |
O4—C4—C3 | 110.84 (12) | C3'—C4'—H4' | 109.0 |
C5—C4—C3 | 108.61 (12) | C5'—C4'—H4' | 109.0 |
O4—C4—H4 | 109.5 | O5'—C5'—C6' | 108.95 (12) |
C5—C4—H4 | 109.5 | O5'—C5'—C4' | 107.00 (12) |
C3—C4—H4 | 109.5 | C6'—C5'—C4' | 113.60 (12) |
O5—C5—C6 | 107.34 (12) | O5'—C5'—H5' | 109.1 |
O5—C5—C4 | 109.96 (12) | C6'—C5'—H5' | 109.1 |
C6—C5—C4 | 112.49 (12) | C4'—C5'—H5' | 109.1 |
O5—C5—H5 | 109.0 | O6'—C6'—C5' | 113.30 (12) |
C6—C5—H5 | 109.0 | O6'—C6'—H6'1 | 108.9 |
C4—C5—H5 | 109.0 | C5'—C6'—H6'1 | 108.9 |
O6—C6—C5 | 109.10 (12) | O6'—C6'—H6'2 | 108.9 |
O6—C6—H6A | 109.9 | C5'—C6'—H6'2 | 108.9 |
C5—C6—H6A | 109.9 | H6'1—C6'—H6'2 | 107.7 |
O6—C6—H6B | 109.9 | O1'—C7'—H7'1 | 109.5 |
C5—C6—H6B | 109.9 | O1'—C7'—H7'2 | 109.5 |
H6A—C6—H6B | 108.3 | H7'1—C7'—H7'2 | 109.5 |
C1—O1—C4' | 114.60 (12) | O1'—C7'—H7'3 | 109.5 |
C2—O2—H2O | 108.3 (17) | H7'1—C7'—H7'3 | 109.5 |
C3—O3—H3O | 109.2 (19) | H7'2—C7'—H7'3 | 109.5 |
C4—O4—H4O | 110 (2) | C1'—O1'—C7' | 112.56 (13) |
C1—O5—C5 | 111.84 (11) | C2'—O2'—H2'O | 110.8 (19) |
C6—O6—H6O | 104.7 (19) | C3'—O3'—H3'O | 108 (2) |
O1'—C1'—O5' | 108.40 (12) | C5'—O5'—C1' | 112.14 (11) |
O1'—C1'—C2' | 109.35 (12) | C6'—O6'—H6'O | 103 (2) |
O5'—C1'—C2' | 109.18 (12) | | |
| | | |
O1—C1—C2—O2 | 66.77 (15) | O5'—C1'—C2'—O2' | −178.72 (12) |
O5—C1—C2—O2 | −176.11 (12) | O1'—C1'—C2'—C3' | 174.59 (12) |
O1—C1—C2—C3 | −172.56 (12) | O5'—C1'—C2'—C3' | 56.15 (16) |
O5—C1—C2—C3 | −55.44 (16) | O2'—C2'—C3'—O3' | 60.81 (16) |
O2—C2—C3—O3 | −64.15 (15) | C1'—C2'—C3'—O3' | −173.45 (12) |
C1—C2—C3—O3 | 176.27 (11) | O2'—C2'—C3'—C4' | −177.89 (12) |
O2—C2—C3—C4 | 172.93 (12) | C1'—C2'—C3'—C4' | −52.15 (16) |
C1—C2—C3—C4 | 53.35 (16) | C1—O1—C4'—C3' | 111.14 (13) |
O3—C3—C4—O4 | −57.12 (16) | C1—O1—C4'—C5' | −127.43 (13) |
C2—C3—C4—O4 | 64.49 (15) | O3'—C3'—C4'—O1 | −63.59 (15) |
O3—C3—C4—C5 | −176.71 (12) | C2'—C3'—C4'—O1 | 176.57 (12) |
C2—C3—C4—C5 | −55.10 (16) | O3'—C3'—C4'—C5' | 174.58 (12) |
O4—C4—C5—O5 | −62.13 (14) | C2'—C3'—C4'—C5' | 54.74 (16) |
C3—C4—C5—O5 | 58.67 (15) | O1—C4'—C5'—O5' | −179.94 (11) |
O4—C4—C5—C6 | 57.44 (16) | C3'—C4'—C5'—O5' | −59.73 (15) |
C3—C4—C5—C6 | 178.24 (12) | O1—C4'—C5'—C6' | 59.79 (17) |
O5—C5—C6—O6 | −58.02 (16) | C3'—C4'—C5'—C6' | 180.00 (13) |
C4—C5—C6—O6 | −179.10 (12) | O5'—C5'—C6'—O6' | −69.22 (16) |
O5—C1—O1—C4' | 93.89 (13) | C4'—C5'—C6'—O6' | 49.94 (18) |
C2—C1—O1—C4' | −146.19 (12) | O5'—C1'—O1'—C7' | −73.32 (16) |
O1—C1—O5—C5 | 179.10 (12) | C2'—C1'—O1'—C7' | 167.74 (13) |
C2—C1—O5—C5 | 60.83 (16) | C6'—C5'—O5'—C1' | −170.76 (12) |
C6—C5—O5—C1 | 174.66 (12) | C4'—C5'—O5'—C1' | 66.04 (15) |
C4—C5—O5—C1 | −62.68 (15) | O1'—C1'—O5'—C5' | 175.95 (13) |
O1'—C1'—C2'—O2' | −60.27 (17) | C2'—C1'—O5'—C5' | −65.01 (15) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2O···O2′i | 0.83 (3) | 1.97 (3) | 2.8042 (19) | 175 (2) |
O3—H3O···O6ii | 0.74 (3) | 1.93 (3) | 2.6580 (19) | 167 (2) |
O4—H4O···O6′iii | 0.82 (2) | 2.03 (2) | 2.8475 (16) | 174 (2) |
O6—H6O···O3iv | 0.79 (3) | 1.91 (3) | 2.6713 (19) | 163 (2) |
O2′—H2′O···O2i | 0.80 (3) | 2.03 (3) | 2.8263 (19) | 169 (2) |
O3′—H3′O···O2 | 0.78 (3) | 2.42 (2) | 3.1357 (17) | 153 (2) |
O3′—H3′O···O3′i | 0.78 (3) | 2.43 (3) | 2.9719 (19) | 127 (2) |
O6′—H6′O···O5 | 0.76 (3) | 2.30 (3) | 3.0046 (15) | 157 (2) |
O6′—H6′O···O6 | 0.76 (3) | 2.52 (2) | 3.0817 (17) | 133 (2) |
Symmetry codes: (i) x+1/2, −y+3/2, −z; (ii) −x+1, y+1/2, −z+1/2; (iii) −x+2, y+1/2, −z+1/2; (iv) −x+2, y−1/2, −z+1/2. |
Experimental details
Crystal data |
Chemical formula | C13H24O11 |
Mr | 356.32 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 100 |
a, b, c (Å) | 4.7087 (4), 14.1428 (12), 23.2401 (19) |
V (Å3) | 1547.7 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.14 |
Crystal size (mm) | 0.35 × 0.07 × 0.05 |
|
Data collection |
Diffractometer | Bruker X8-APEX-II CCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13853, 2964, 2644 |
Rint | 0.031 |
(sin θ/λ)max (Å−1) | 0.734 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.033, 0.088, 1.04 |
No. of reflections | 2964 |
No. of parameters | 246 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.45, −0.21 |
Absolute structure | Flack (1983), 2143 Friedel pairs |
Absolute structure parameter | 0.5 (7) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2O···O2'i | 0.83 (3) | 1.97 (3) | 2.8042 (19) | 175 (2) |
O3—H3O···O6ii | 0.74 (3) | 1.93 (3) | 2.6580 (19) | 167 (2) |
O4—H4O···O6'iii | 0.82 (2) | 2.03 (2) | 2.8475 (16) | 174 (2) |
O6—H6O···O3iv | 0.79 (3) | 1.91 (3) | 2.6713 (19) | 163 (2) |
O2'—H2'O···O2i | 0.80 (3) | 2.03 (3) | 2.8263 (19) | 169 (2) |
O3'—H3'O···O2 | 0.78 (3) | 2.42 (2) | 3.1357 (17) | 153 (2) |
O3'—H3'O···O3'i | 0.78 (3) | 2.43 (3) | 2.9719 (19) | 127 (2) |
O6'—H6'O···O5 | 0.76 (3) | 2.30 (3) | 3.0046 (15) | 157 (2) |
O6'—H6'O···O6 | 0.76 (3) | 2.52 (2) | 3.0817 (17) | 133 (2) |
Symmetry codes: (i) x+1/2, −y+3/2, −z; (ii) −x+1, y+1/2, −z+1/2; (iii) −x+2, y+1/2, −z+1/2; (iv) −x+2, y−1/2, −z+1/2. |
Comparison of structural parameters in (I) and (II). topParameter | (I) | (II) |
Bond lengths (Å) | | |
C1-C2 | 1.527 (3) | 1.528 (2) |
C1'-C2' | 1.516 (3) | 1.534 (2) |
C1-O5 | 1.425 (3) | 1.4293 (17) |
C1'-O5' | 1.413 (3) | 1.4352 (18) |
C1-O1 | 1.387 (3) | 1.3988 (18) |
C1'-O1' | 1.384 (3) | 1.3821 (18) |
C4'-O1 | 1.437 (3) | 1.4390 (17) |
C2-O2 | 1.414 (3) | 1.4313 (17) |
C4-O4 | 1.423 (3) | 1.4268 (18) |
C6-O6 | 1.426 (3) | 1.4392 (18) |
C2'-O2' | 1.418 (3) | 1.4252 (17) |
C5-C6 | 1.511 (3) | 1.516 (2) |
C5'-C6' | 1.508 (3) | 1.519 (2) |
O3'-O5 | 2.764 | |
O(CH3OH)-O6' | 2.727 | |
O6'-O5 | | 3.0053 (16) |
O6'-O6 | | 3.0819 (17) |
O3'-O2 | | 3.1363 (17) |
Bond angles (°) | | |
C1-O1-C4' | 116.2 (2) | 114.60 (12) |
C1'-O1'-CH3 | 113.7 (2) | 112.56 (13) |
O3'-H3'O-O5 | 140.9 | |
O-H(CH3OH)-O6' | 164.4 | |
O6'-H6'O-O5 | | 156.9 |
O6'-H6'O-O6 | | 133.3 |
O3'-H3'O-O2 | | 152.9 |
Torsion angles (°) | | |
C1-C2-C3-C4 | -54.8 (2) | 53.35 (16) |
C1'-C2'-C3'-C4' | -44.2 (3) | -52.15 (16) |
C1-O5-C5-C4 | 65.0 (2) | -62.68 (15) |
C1'-O5'-C5'-C4' | 67.6 (2) | 66.04 (15) |
C2-C1-O1-C4'(ϕ) | 153.8 (2) | -146.19 (12) |
C2'-C1'-O1'-CH3(ϕ') | 164.2 (2) | 167.74 (13) |
C1-O1-C4'-C3'(ψ) | 78.4 (2) | 111.14 (13) |
C1-O1-C4'-C5'(ψ) | -161.3 (2) | -127.43 (13) |
O5-C1-O1-C4'(ϕ) | -88.4 (2) | 93.89 (13) |
O5'-C1'-O1'-CH3(ϕ') | -77.4 (3) | -73.32 (16) |
H1-C1-O1-C4'(ϕ) | 31.9 | -25.6 |
C1-O1-C4'-H4'(ψ) | -43.7 | -7.3 |
O5-C5-C6-O6(ω) | 57.3 (2)(gt) | -58.02 (16)(gt) |
O5'-C5'-C6'-O6'(ω') | -54.6 (2)(gg) | -69.22 (16)(gg) |
Structural studies of di- and oligosaccharides have focused to a large extent on O-glycosidic linkages observed in nature. For example, crystal structures of β-D-Gal-(1→4)-α- and β-D-GlcOCH3 (I) (Stenutz et al., 1999; Pan et al., 2005) and related β-(1→4) linkages such as found in β-D-Glc-(1→4)-β-D-GlcOCH3 (Ham & Williams, 1970) and β-D-GlcNAc-(1→4)-β-D-GlcNAc (Mo & Jensen, 1978) have been investigated, and all contain linkage interfaces between aldopyranosyl rings having the D-configuration (Gal is galactose and Glu is glucose). As expected, these disaccharides display common structural motifs dictated by their shared linkage type. For example, β-(1→4) linkages involving D-sugars typically show inter-residue hydrogen bonds between O3'H and O5 as shown in the first scheme below for (I). Thus, it may be inferred that efforts aimed at identifying the various structural factors influencing O-glycosidic linkage conformations using natural systems will necessarily reveal only a subset of the possible interface interactions. One way to modulate the linkage interface and the overall molecular topology is to substitute an L-sugar for a D-sugar while retaining the relative configuration of the substituted residue. This perturbation has been introduced into the structure of β-D-Gal-(1→4)-β-D-GlcOCH3 (methyl β-lactoside; D-LAC), (I), by substituting β-L-Gal at the β-D-Gal residue, yielding β-L-Gal-(1→4)-β-D-GlcOCH3 (methyl β-L-lactoside; L-LAC), (II).
Unlike D-LAC, L-LAC crystallizes solvent-free from methanol (Fig. 1). A comparison of representative molecular parameters for (I) and (II) is shown in Table 1. The bond lengths in (I) and (II) are, on average, similar, although some significant differences exist (e.g. C1'—O5' and C2—O2). The C1—O1—C4' bond angle is slightly smaller in L-LAC, and this angle is larger than the C1'— O1'—CH3 glycosidic bond angle in both structures.
Intra-ring torsion angles C1—C2—C3—C4 and C1'—C2'—C3'—C4' deviate significantly from the idealized values of 60°. This deviation is smaller for the intra-ring C1—O5—C5—C4 and C1'—O5'—C5'—C4' torsion angles, suggesting that aldopyranosyl ring distortions result mainly from reduced C—C—C—C torsions. Glycosidic torsion angles ϕ are very similar in (I) and (II), as indicated by the similar absolute values of the C2—C1—O1—C4', O5—C1—O1—C4' and H1—C1—O1—C4' torsion angles. In both structures, the ϕ torsion angle is consistent with expectations based on stereoelectronic factors (the exo-anomeric effect; C2 roughly anti to C4') (Lemieux, 1971; Juaristi & Cuevas, 1995). In contrast, the glycosidic torsion angle ψ differs by ~34° between (I) and (II). Interestingly, in (II), ψ assumes a nearly eclipsed conformation [–127.43 (13)°] in contrast to the more nearly staggered conformation observed in (I) [–161.3 (2)°], indicating that significant deviations from staggered conformations are possible in glycosidic linkages. This finding contrasts sharply with other mobile exocyclic bonds in saccharides (e.g. C5—C6 bonds in aldohexopyranosyl rings) where staggered or nearly staggered rotamers are energetically more stable than the eclipsed or near eclipsed rotamers (Thibaudeau et al., 2004). Hydroxymethyl conformations in the Gal (gt) and Glc (gg) residues are the same in both structures.
The change in absolute configuration of the Gal residue affects the linkage interface significantly. In D-LAC, atoms O3' and O5 are in close proximity (2.76 Å), and an inter-residue hydrogen bond between the O3'/H group and atom O5 is observed in the crystal structure. In L-LAC, atoms O6' and O5 are in close proximity [3.0053 (16) Å], and an inter-residue hydrogen bond between the O6'/H group and atom O5 (Scheme 1) is observed. Furthermore, atom O6' is close to atom O6 [3.0819 (17) Å], atom O3' is close to atom O2 [3.1363 (17) Å], and two additional hydrogen bonds are observed, with O6'/H and O3'/H serving as donors (Scheme 1). Thus, in (II), the O6'/H group participates in two hydrogen bonds with atoms O5 and O6 (a three-center hydrogen-bond system).
Recent NMR investigations of (I) indicate the presence of hydrogen bonding between the O3'/H group and atom O5 in a water/acetone solvent at 253 K based on the behavior of the 3JHCOH and 3JCCOH values (Zhao et al., 2005). NMR studies of (I) in aqueous solution indicate a mixture of gg and gt hydroxymethyl rotamers in the Glc residue based on the analysis of 3JHH values, (Hayes et al., 1982). If hydrogen bonding between atoms O6' and O5 of (II) exists in water/acetone solvent, not only might the 3JHCOH and 3JCCOH values involving O6'/H be affected, but possibly the distribution of gg and gt rotamers in the Glc residue, with a shift towards the gg state expected. Furthermore, comparisons of trans-glycoside J-couplings in D-LAC and L-LAC may establish whether ψ is shifted in solution in a manner similar to that observed in the crystal. The results of these NMR investigations will be reported elsewhere.
The crystal structure is a three-dimensional hydrogen-bonded network composed of two-dimensional sheets that are staggered to form columns in a three-dimensional lattice. In the sheets, which are formed from a 6,3-network parallel to (100), each molecule is connected to three additional molecules via two, two and three hydrogen bonds, respectively. Additional hydrogen bonding connects each molecule to three complementary molecules through two, one and one hydrogen bonds to extend the structure into alternating columns parallel to the a axis. While there is no hydrogen bonding between molecules of a given column, hydrogen bonds exist between molecules of neighboring columns. These alternating columns are slipped with respect to each other by 1/2 translation along the a axis. Details of the hydrogen bonding are given in Table 2, and a representative view is shown in Fig. 2. A view emphasizing the columnar packing is shown in Fig. 3.
Intermolecular hydrogen-bonding patterns observed for (II) are very similar, but not identical, to those found for natural disaccharides (Pan et al., 2005). Thus, atoms O1', O5' and O1 do not participate as hydrogen-bond acceptors. All hydroxy H atoms are involved in hydrogen bonding, and most hydroxy O atoms participate in either zero (O4) or one (O2', O6', O2, O3 and O6) hydrogen bond as acceptors.
The glycosidic linkage in (II) is a structural mimic of linkages involving the biologically important β-L-fucopyranosyl ring, (III), and a crystal structure of methyl β-L-fucopyranosyl-(1→3)-α-D-glucopyranoside trihydrate has been reported recently (Färnbäck et al., 2003). In di- and oligosaccharides containing (III), however, potential inter-residue hydrogen bonding is more restricted than for L-Gal, since the L-Fuc ring lacks a hydroxy group at atom C6.
In addition to its modified glycosidic linkage interface, L-LAC displays an overall contact surface very different from that of D-LAC. An identical but mirror-image contact surface (and linkage interface) would be generated in the alternate L-LAC structure composed of D-Gal and L-Glc residues. Because both the linkage interface and surface topology are affected by L-sugar substitution, this derivatization may prove generally useful in the design of saccharide-based biological agents or pharmaceuticals having novel binding properties or functions.