organic compounds
6-Deoxy-6-fluoro-D-galactose
aDepartment of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England, bRare Sugar Research Centre, Kagawa University, 2393 Miki-cho, Kita-gun, Kagawa 761-0795, Japan, cSummit PLC, 91 Milton Park, Abingdon, Oxon OX14 4RY, England, dDextra Laboratories Ltd, Science and Technology Centre, Whiteknights Road, Reading RG6 6BZ, England, and eDepartment of Chemical Crystallography, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England
*Correspondence e-mail: sarah.jenkinson@chem.ox.ac.uk
The 6H11FO5. The absolute stereochemistry was determined by the use of D-galactose as the starting material. The compound exists as a three-dimensional O—H⋯O hydrogen-bonded network with each molecule acting as a donor and acceptor for four hydrogen bonds.
unequivocally confirms the relative stereochemistry of the title compound, CRelated literature
For literature relating to the biotechnological interconversion of et al. (2004); Izumori (2006); Jones et al. (2008); Rao et al. (2009); Jenkinson et al. (2009); Gullapalli et al. (2010). For literature relating to fluorosugars, see: Cobb et al. (2005); Caravano et al. (2009); Brackhagen et al. (2001); Taylor & Kent (1958).
(Izumoring), see: GranströmExperimental
Crystal data
|
Refinement
|
Data collection: COLLECT (Nonius, 2001); cell DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.
Supporting information
https://doi.org/10.1107/S1600536810016612/lh5035sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810016612/lh5035Isup2.hkl
The title compound was recrystallised by vapour diffusion from a mixture of ethanol and water [m.p. 431-433 K;[α]D25 initial: +119.8, equilibrium: +69.4 (c 1.12, H2O) {Lit. (Taylor & Kent, 1958) m.p. 433 K; [α]D20 initial: +135, equilibrium: +76.5 (c 0.967, H2O)].
In the absence of significant
Friedel pairs were merged and the was assigned from the use of D-galactose as the starting material.The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, O—H = 0.82 Å) and Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom), after which the positions were refined with riding constraints.
Izumoring, a strategy for the biotechnological interconversion of
and (Granström et al. 2004, Izumori 2006) allows convenient access to rare Interconversions are achieved by regioselective microbial oxidation of to give the corresponding followed by enzymatic isomerisation to Stereochemical diversity is introduced at C-2 in the keto-aldose isomerisation step and at C-3 by the epimerisation of catalysed by D-tagatose-3-epimerase. In addition to the simple this strategy is effective for the interconversion of deoxy (Gullapalli et al. 2010, Rao et al. 2009), methyl-branched (Jones et al. 2008) and azido (Jenkinson et al. 2009) sugars.Fluorosugars have not been isolated from natural sources and consequently, in order to study metabolic processes, their passage along various biological pathways can be effectively tracked with the detection of fluorinated metabolites by 19F NMR (Cobb et al. 2005). The fluoro modification of sugars affects their hydrogen bonding capability and fluorosugars have been shown to resemble deoxy sugars such as fucose and rhamnose in terms of enzymatic recognition (Caravano et al. 2009). Application of the Izumoring strategy to fluorinated substrates would allow the bulk preparation of fluorosugars, an important and interesting class of carbohydrates.
6-Deoxy-6-fluoro-D-galactose was prepared from D-galactose diacetonide 1 (Fig. 1). Fluoride was introduced nucleophilically to give the protected fluorogalactose 2 in 68% yield as previously described for the
(Brackhagen et al. 2001). Dowex resin (H+) catalysed hydrolysis of the diacetonide gave the free 6-deoxy-6-fluoro-D-galactose 3 in 98% yield.X-ray crystallography unequivocally confirmed the relative stereochemistry of the title compound. The absolute stereochemistry was determined by the use of D-galactose as the starting material. The compound exists as an extensively hydrogen-bonded lattice with each molecule acting as a donor and acceptor for 4 hydrogen bonds. Only classical hydrogen bonding is considered.
For literature relating to the biotechnological interconversion of
(Izumoring) see: Granström et al. (2004); Izumori (2006); Jones et al. (2008); Rao et al. (2009); Jenkinson et al. (2009); Gullapalli et al. (2010). For literature relating to fluorosugars see: Cobb et al. (2005); Caravano et al. (2009); Brackhagen et al. (2001); Taylor & Kent (1958).Data collection: COLLECT (Nonius, 2001); cell
DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS (Betteridge et al., 2003).C6H11FO5 | F(000) = 384 |
Mr = 182.15 | Dx = 1.664 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 976 reflections |
a = 6.7928 (3) Å | θ = 5–27° |
b = 7.5822 (3) Å | µ = 0.16 mm−1 |
c = 14.1165 (6) Å | T = 150 K |
V = 727.06 (5) Å3 | Plate, colourless |
Z = 4 | 0.25 × 0.15 × 0.15 mm |
Area diffractometer | 855 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.082 |
ω scans | θmax = 27.4°, θmin = 5.1° |
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997) | h = −8→8 |
Tmin = 0.88, Tmax = 0.98 | k = −9→9 |
6912 measured reflections | l = −18→18 |
978 independent reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.048 | H-atom parameters constrained |
wR(F2) = 0.119 | Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.06P)2 + 0.71P], where P = [max(Fo2,0) + 2Fc2]/3 |
S = 1.00 | (Δ/σ)max = 0.000180 |
978 reflections | Δρmax = 0.39 e Å−3 |
109 parameters | Δρmin = −0.33 e Å−3 |
0 restraints |
C6H11FO5 | V = 727.06 (5) Å3 |
Mr = 182.15 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.7928 (3) Å | µ = 0.16 mm−1 |
b = 7.5822 (3) Å | T = 150 K |
c = 14.1165 (6) Å | 0.25 × 0.15 × 0.15 mm |
Area diffractometer | 978 independent reflections |
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997) | 855 reflections with I > 2σ(I) |
Tmin = 0.88, Tmax = 0.98 | Rint = 0.082 |
6912 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 1.00 | Δρmax = 0.39 e Å−3 |
978 reflections | Δρmin = −0.33 e Å−3 |
109 parameters |
x | y | z | Uiso*/Ueq | ||
F1 | 0.9642 (3) | 0.0074 (3) | 0.67642 (15) | 0.0322 | |
C2 | 0.8064 (5) | 0.1203 (4) | 0.7000 (2) | 0.0241 | |
C3 | 0.8368 (5) | 0.2957 (4) | 0.6533 (2) | 0.0197 | |
O4 | 0.8221 (3) | 0.2665 (3) | 0.55221 (14) | 0.0197 | |
C5 | 0.8651 (5) | 0.4205 (4) | 0.4981 (2) | 0.0199 | |
O6 | 1.0586 (3) | 0.4776 (3) | 0.51563 (17) | 0.0249 | |
C7 | 0.7217 (5) | 0.5681 (4) | 0.5230 (2) | 0.0193 | |
O8 | 0.7765 (3) | 0.7197 (3) | 0.46922 (16) | 0.0253 | |
C9 | 0.7242 (5) | 0.6033 (4) | 0.6292 (2) | 0.0196 | |
C10 | 0.6857 (5) | 0.4332 (4) | 0.6843 (2) | 0.0207 | |
O11 | 0.4899 (3) | 0.3738 (3) | 0.66532 (15) | 0.0234 | |
O12 | 0.5874 (3) | 0.7379 (3) | 0.65554 (15) | 0.0225 | |
H21 | 0.6889 | 0.0662 | 0.6738 | 0.0302* | |
H22 | 0.7979 | 0.1319 | 0.7701 | 0.0295* | |
H31 | 0.9723 | 0.3377 | 0.6670 | 0.0229* | |
H51 | 0.8463 | 0.3902 | 0.4278 | 0.0240* | |
H71 | 0.5858 | 0.5333 | 0.5064 | 0.0246* | |
H91 | 0.8539 | 0.6454 | 0.6460 | 0.0234* | |
H101 | 0.7044 | 0.4557 | 0.7541 | 0.0250* | |
H121 | 0.4980 | 0.7488 | 0.6170 | 0.0346* | |
H111 | 0.4489 | 0.3361 | 0.7175 | 0.0347* | |
H61 | 1.1320 | 0.3983 | 0.4931 | 0.0374* | |
H81 | 0.7170 | 0.8119 | 0.4811 | 0.0389* |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0339 (11) | 0.0274 (10) | 0.0352 (11) | 0.0100 (9) | 0.0011 (9) | 0.0051 (9) |
C2 | 0.0227 (16) | 0.0222 (15) | 0.0273 (15) | 0.0057 (15) | 0.0012 (14) | 0.0016 (13) |
C3 | 0.0187 (14) | 0.0211 (14) | 0.0193 (14) | 0.0019 (13) | 0.0003 (12) | 0.0014 (12) |
O4 | 0.0221 (11) | 0.0165 (10) | 0.0205 (10) | −0.0024 (9) | 0.0011 (9) | 0.0005 (9) |
C5 | 0.0189 (15) | 0.0168 (14) | 0.0241 (14) | −0.0029 (12) | 0.0029 (12) | 0.0020 (12) |
O6 | 0.0193 (12) | 0.0195 (10) | 0.0359 (12) | 0.0006 (9) | 0.0060 (10) | −0.0002 (9) |
C7 | 0.0205 (16) | 0.0171 (14) | 0.0204 (14) | 0.0006 (12) | 0.0028 (12) | 0.0018 (12) |
O8 | 0.0307 (12) | 0.0176 (10) | 0.0277 (11) | 0.0021 (10) | 0.0077 (10) | 0.0035 (9) |
C9 | 0.0172 (15) | 0.0171 (14) | 0.0246 (15) | 0.0033 (13) | 0.0001 (12) | −0.0020 (12) |
C10 | 0.0192 (16) | 0.0228 (15) | 0.0203 (14) | 0.0005 (13) | −0.0016 (12) | 0.0012 (12) |
O11 | 0.0185 (11) | 0.0281 (12) | 0.0236 (11) | −0.0034 (10) | 0.0013 (9) | 0.0023 (10) |
O12 | 0.0220 (11) | 0.0230 (11) | 0.0226 (10) | 0.0054 (10) | −0.0005 (9) | −0.0038 (10) |
F1—C2 | 1.412 (4) | C7—O8 | 1.428 (4) |
C2—C3 | 1.499 (4) | C7—C9 | 1.522 (4) |
C2—H21 | 0.971 | C7—H71 | 0.988 |
C2—H22 | 0.995 | O8—H81 | 0.824 |
C3—O4 | 1.448 (3) | C9—C10 | 1.528 (4) |
C3—C10 | 1.527 (4) | C9—O12 | 1.430 (4) |
C3—H31 | 0.992 | C9—H91 | 0.967 |
O4—C5 | 1.426 (4) | C10—O11 | 1.430 (4) |
C5—O6 | 1.406 (4) | C10—H101 | 1.008 |
C5—C7 | 1.524 (4) | O11—H111 | 0.838 |
C5—H51 | 1.027 | O12—H121 | 0.820 |
O6—H61 | 0.843 | ||
F1—C2—C3 | 109.2 (3) | C5—C7—C9 | 110.4 (2) |
F1—C2—H21 | 106.2 | O8—C7—C9 | 112.3 (2) |
C3—C2—H21 | 108.7 | C5—C7—H71 | 110.3 |
F1—C2—H22 | 109.4 | O8—C7—H71 | 109.4 |
C3—C2—H22 | 111.5 | C9—C7—H71 | 106.9 |
H21—C2—H22 | 111.7 | C7—O8—H81 | 116.5 |
C2—C3—O4 | 106.8 (2) | C7—C9—C10 | 110.5 (3) |
C2—C3—C10 | 112.8 (3) | C7—C9—O12 | 112.0 (2) |
O4—C3—C10 | 109.9 (2) | C10—C9—O12 | 111.0 (2) |
C2—C3—H31 | 109.1 | C7—C9—H91 | 108.1 |
O4—C3—H31 | 107.8 | C10—C9—H91 | 108.0 |
C10—C3—H31 | 110.3 | O12—C9—H91 | 107.0 |
C3—O4—C5 | 112.9 (2) | C9—C10—C3 | 108.4 (3) |
O4—C5—O6 | 110.4 (3) | C9—C10—O11 | 109.2 (3) |
O4—C5—C7 | 110.3 (2) | C3—C10—O11 | 110.9 (3) |
O6—C5—C7 | 109.3 (2) | C9—C10—H101 | 109.5 |
O4—C5—H51 | 108.0 | C3—C10—H101 | 108.1 |
O6—C5—H51 | 110.8 | O11—C10—H101 | 110.7 |
C7—C5—H51 | 107.9 | C10—O11—H111 | 104.6 |
C5—O6—H61 | 105.5 | C9—O12—H121 | 112.3 |
C5—C7—O8 | 107.6 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H21···O12i | 0.97 | 2.60 | 3.318 (4) | 131 |
C5—H51···O11ii | 1.03 | 2.59 | 3.320 (4) | 128 |
O12—H121···O8iii | 0.82 | 1.95 | 2.769 (4) | 177 |
O11—H111···O12iv | 0.84 | 1.96 | 2.781 (4) | 168 |
O6—H61···O4ii | 0.84 | 1.91 | 2.747 (4) | 174 |
O8—H81···O6iii | 0.82 | 1.93 | 2.739 (4) | 169 |
Symmetry codes: (i) x, y−1, z; (ii) x+1/2, −y+1/2, −z+1; (iii) x−1/2, −y+3/2, −z+1; (iv) −x+1, y−1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C6H11FO5 |
Mr | 182.15 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 150 |
a, b, c (Å) | 6.7928 (3), 7.5822 (3), 14.1165 (6) |
V (Å3) | 727.06 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.16 |
Crystal size (mm) | 0.25 × 0.15 × 0.15 |
Data collection | |
Diffractometer | Area |
Absorption correction | Multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997) |
Tmin, Tmax | 0.88, 0.98 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6912, 978, 855 |
Rint | 0.082 |
(sin θ/λ)max (Å−1) | 0.648 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.119, 1.00 |
No. of reflections | 978 |
No. of parameters | 109 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.39, −0.33 |
Computer programs: COLLECT (Nonius, 2001), DENZO/SCALEPACK (Otwinowski & Minor, 1997), SIR92 (Altomare et al., 1994), CRYSTALS (Betteridge et al., 2003), CAMERON (Watkin et al., 1996).
D—H···A | D—H | H···A | D···A | D—H···A |
O12—H121···O8i | 0.82 | 1.95 | 2.769 (4) | 177 |
O11—H111···O12ii | 0.84 | 1.96 | 2.781 (4) | 168 |
O6—H61···O4iii | 0.84 | 1.91 | 2.747 (4) | 174 |
O8—H81···O6i | 0.82 | 1.93 | 2.739 (4) | 169 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+1, y−1/2, −z+3/2; (iii) x+1/2, −y+1/2, −z+1. |
References
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Izumoring, a strategy for the biotechnological interconversion of aldoses, ketoses and alditols (Granström et al. 2004, Izumori 2006) allows convenient access to rare monosaccharides. Interconversions are achieved by regioselective microbial oxidation of alditols to give the corresponding ketoses, followed by enzymatic isomerisation to aldoses. Stereochemical diversity is introduced at C-2 in the keto-aldose isomerisation step and at C-3 by the epimerisation of ketoses, catalysed by D-tagatose-3-epimerase. In addition to the simple monosaccharides, this strategy is effective for the interconversion of deoxy (Gullapalli et al. 2010, Rao et al. 2009), methyl-branched (Jones et al. 2008) and azido (Jenkinson et al. 2009) sugars.
Fluorosugars have not been isolated from natural sources and consequently, in order to study metabolic processes, their passage along various biological pathways can be effectively tracked with the detection of fluorinated metabolites by 19F NMR (Cobb et al. 2005). The fluoro modification of sugars affects their hydrogen bonding capability and fluorosugars have been shown to resemble deoxy sugars such as fucose and rhamnose in terms of enzymatic recognition (Caravano et al. 2009). Application of the Izumoring strategy to fluorinated substrates would allow the bulk preparation of fluorosugars, an important and interesting class of carbohydrates.
6-Deoxy-6-fluoro-D-galactose was prepared from D-galactose diacetonide 1 (Fig. 1). Fluoride was introduced nucleophilically to give the protected fluorogalactose 2 in 68% yield as previously described for the enantiomer (Brackhagen et al. 2001). Dowex resin (H+) catalysed hydrolysis of the diacetonide gave the free 6-deoxy-6-fluoro-D-galactose 3 in 98% yield.
X-ray crystallography unequivocally confirmed the relative stereochemistry of the title compound. The absolute stereochemistry was determined by the use of D-galactose as the starting material. The compound exists as an extensively hydrogen-bonded lattice with each molecule acting as a donor and acceptor for 4 hydrogen bonds. Only classical hydrogen bonding is considered.