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Acta Cryst. (2008). E64, o1010-o1011    [ doi:10.1107/S1600536808012555 ]

1-Deoxy-D-arabinitol

S. F. Jenkinson, F. P. Cruz, K. V. Booth, G. W. J. Fleet, K. Izumori, C.-Y. Yu and D. J. Watkin

Abstract top

Addition of methyl lithium to D-erythrono-1,4-lactone followed by acid deprotection was shown, by X-ray crystallography, to give 1-deoxy-D-arabinitol, C5H12O4, rather than 1-deoxy-D-ribitol as the major product. The crystal structure exists as hydrogen-bonded chains of molecules running parallel to the c axis which are further linked together by hydrogen bonds. Each molecule is a donor and an acceptor for four hydrogen bonds.

Comment top

The demand for the large scale production of rare sugars by biotechnological (Izumori, 2006; Izumori, 2002; Granstrom et al., 2004) and chemical (Beadle et al., 1992) methods is driven by the demand for alternative foodstuffs (Skytte, 2002) and D-tagatose itself is used as a low calorie sweetener (Levin, 2002; Howling & Callagan, 2000; Bertelsen et al. 1999) Rare monosaccharides have been found to demonstrate interesting pharmaceutical properties, for example, D-psicose (Takata et al., 2005; Menavuvu et al., 2006) and D-allose (Sui et al., 2005; Hossain et al., 2006) have significant chemotherapeutic properties and D-tagatose has been found to be an anti-hyperglycemic agent (Zehner et al., 1994; Donner et al., 1999) and therefore potentially useful in the treatment of diabetes.

The methodology developed by Izumori et al. (2002, 2006) for the interconversion of tetroses, pentoses and hexoses by enzymatic oxidation, inversion at C3 with a single epimerase, and reduction to the aldose has been seen to be generally applicable for the 1-deoxy ketohexoses (Yoshihara et al., 2008). In order to investigate the viability of this process to the corresponding pentoses and thus to evaluate their therapeutic potential 1-deoxy-D-arabinitol was synthesized, in 3 steps, from 2,3-O-isopropylidene-D-erythronolactone 1 (Fig.1). It has previously been seen that the four diastereomeric tetraols are very difficult to distinguish between by NMR spectroscopy (Takai & Heathcock, 1985). X-ray crystallography confirmed that the major product was the arabinitol 4 rather than the ribitol 3 which differs only in the stereochemistry at the C2 position (Fig. 2).

The molecules are linked by three hydrogen bonding systems and the structure consists of alternating spiral chains of O6—H6···O6 or O8—H8···O8 hydrogen-bonded molecules running parallel to the c-axis (Fig. 3) interconnected by O1—H1···O4—H4···O1 hydrogen bonds (Fig.4). Each molecule is a donor and acceptor for 4 hydrogen bonds (Fig. 5).

In summary, the stereochemistry at C2 of the title compound 1-deoxy-D-arabinitol 4 was firmly established by X-ray crystallography, the absolute configuration is determined by the use of D-erythronolactone as the starting material. As well as the potential biological properties of 1-deoxy ketoses, they are likely to provide a new set of building blocks for the synthesis of a wide variety of complex biomolecules.

Related literature top

For related literature see: Izumori (2002, 2006); Granstrom et al. (2004); Beadle et al. (1992); Skytte (2002); Levin (2002); Howling & Callagan (2000); Bertelsen et al. (1999); Takata et al. (2005); Menavuvu et al. (2006); Sui et al. (2005); Hossain et al. (2006); Zehner et al. (1994); Donner et al. (1999); Yoshihara et al. (2008); Takai & Heathcock (1985); Zissis & Richtmyer (1954).

Experimental top

The title compound was recrystallized from hot methanol: m.p. 398–400 K; [α]D21 +0.8 (c, 8 in H2O) {Lit. (Zissis & Richtmyer, 1954) m.p. 129–131°C; [α]D20 +0.7 (c, 10 in H2O; l, 4)}.

Refinement top

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration assigned from 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.

Computing details top

Data collection: COLLECT (Nonius, 2001); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. Synthetic scheme.
[Figure 2] Fig. 2. The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
[Figure 3] Fig. 3. Packing diagram showing the O6—H6···O6 and O8—H8···O8 hydrogen bonds.
[Figure 4] Fig. 4. Packing diagram showing the O1—H1···O4—H4···O1 hydrogen bonds.
[Figure 5] Fig. 5. Packing diagram for the compound projected along the c-axis. Each molecule is a donor and an acceptor for 4 hydrogen-bonds.
1-Deoxy-D-arabinitol top
Crystal data top
C5H12O4Z = 8
Mr = 136.15F000 = 592
Tetragonal, I41Dx = 1.281 Mg m−3
Hall symbol: I 4bwMo Kα radiation
λ = 0.71073 Å
a = 12.9873 (5) ÅCell parameters from 815 reflections
b = 12.9873 (5) Åθ = 5–27º
c = 8.3679 (3) ŵ = 0.11 mm−1
α = 90ºT = 150 K
β = 90ºBlock, colourless
γ = 90º0.25 × 0.25 × 0.25 mm
V = 1411.41 (9) Å3
Data collection top
Nonius KappaCCD area-detector
diffractometer		750 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.020
T = 150 Kθmax = 27.5º
ω scansθmin = 5.3º
Absorption correction: multi-scan
(DENZO/SCALEPACK; Otwinowski & Minor, 1997)		h = −16→16
Tmin = 0.93, Tmax = 0.97k = −11→11
3189 measured reflectionsl = −10→10
855 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.123  w = 1/[σ2(F2) + ( 0.07P)2 + 1.26P],
where P = (max(Fo2,0) + 2Fc2)/3
S = 1.00(Δ/σ)max = 0.002
855 reflectionsΔρmax = 0.34 e Å−3
82 parametersΔρmin = −0.39 e Å−3
1 restraintExtinction correction: None
Crystal data top
C5H12O4γ = 90º
Mr = 136.15V = 1411.41 (9) Å3
Tetragonal, I41Z = 8
a = 12.9873 (5) ÅMo Kα
b = 12.9873 (5) ŵ = 0.11 mm−1
c = 8.3679 (3) ÅT = 150 K
α = 90º0.25 × 0.25 × 0.25 mm
β = 90º
Data collection top
Nonius KappaCCD area-detector
diffractometer		855 independent reflections
Absorption correction: multi-scan
(DENZO/SCALEPACK; Otwinowski & Minor, 1997)		750 reflections with I > 2σ(I)
Tmin = 0.93, Tmax = 0.97Rint = 0.020
3189 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.123Δρmax = 0.34 e Å−3
S = 1.00Δρmin = −0.39 e Å−3
855 reflectionsAbsolute structure: ?
82 parametersFlack parameter: ?
1 restraintRogers parameter: ?
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.64776 (13)0.51955 (15)0.6622 (3)0.0211
C20.75127 (18)0.5139 (2)0.6068 (4)0.0186
C30.7537 (2)0.4842 (2)0.4296 (4)0.0187
O40.85700 (13)0.48073 (16)0.3723 (3)0.0237
C50.6897 (2)0.5564 (2)0.3268 (4)0.0235
O60.73116 (15)0.65798 (14)0.3242 (3)0.0250
C70.8135 (2)0.4417 (2)0.7135 (4)0.0208
O80.76689 (14)0.34124 (13)0.7126 (3)0.0216
C90.8162 (3)0.4788 (2)0.8844 (4)0.0371
H210.78530.58220.62860.0184*
H310.72080.41680.41260.0196*
H510.69850.53150.22380.0277*
H520.61910.55420.34750.0271*
H710.88270.43790.66040.0259*
H910.84130.42650.95440.0541*
H920.85950.53960.89580.0548*
H930.74740.49710.92020.0552*
H10.61940.47220.57030.0308*
H80.79750.29440.63790.0334*
H60.74180.67610.43880.0359*
H40.90700.53690.36510.0365*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0197 (10)0.0197 (9)0.0240 (12)0.0010 (7)0.0042 (9)−0.0023 (9)
C20.0139 (13)0.0193 (12)0.0225 (16)−0.0037 (9)0.0006 (12)−0.0001 (13)
C30.0176 (14)0.0167 (12)0.0218 (17)−0.0006 (9)−0.0011 (12)0.0010 (13)
O40.0169 (9)0.0213 (9)0.0329 (14)0.0015 (7)0.0061 (10)0.0035 (10)
C50.0223 (14)0.0269 (15)0.0214 (16)0.0014 (11)0.0013 (13)0.0032 (15)
O60.0308 (11)0.0215 (10)0.0227 (12)0.0025 (8)0.0056 (11)0.0046 (10)
C70.0201 (13)0.0204 (13)0.0218 (16)−0.0035 (10)−0.0045 (13)−0.0004 (13)
O80.0254 (10)0.0189 (10)0.0204 (12)0.0010 (7)0.0049 (10)0.0000 (9)
C90.053 (2)0.0332 (16)0.0253 (15)−0.0023 (15)−0.0149 (15)−0.0036 (13)
Geometric parameters (Å, °) top
O1—C21.424 (3)C5—H510.927
O1—H11.051C5—H520.934
C2—C31.532 (3)O6—H60.997
C2—C71.527 (4)C7—O81.438 (3)
C2—H211.008C7—C91.510 (5)
C3—O41.425 (3)C7—H711.004
C3—C51.520 (4)O8—H80.959
C3—H310.985C9—H910.954
O4—H40.978C9—H920.974
C5—O61.425 (3)C9—H930.972
C2—O1—H193.6C3—C5—H52114.4
O1—C2—C3110.4 (2)O6—C5—H52113.8
O1—C2—C7109.9 (3)H51—C5—H52106.4
C3—C2—C7113.6 (2)C5—O6—H6104.9
O1—C2—H21108.0C2—C7—O8109.4 (2)
C3—C2—H21112.9C2—C7—C9111.7 (2)
C7—C2—H21101.7O8—C7—C9107.7 (3)
C2—C3—O4110.7 (2)C2—C7—H71104.2
C2—C3—C5112.4 (2)O8—C7—H71109.3
O4—C3—C5110.1 (2)C9—C7—H71114.4
C2—C3—H31110.8C7—O8—H8113.9
O4—C3—H31109.4C7—C9—H91111.2
C5—C3—H31103.2C7—C9—H92111.4
C3—O4—H4128.4H91—C9—H92108.7
C3—C5—O6111.9 (2)C7—C9—H93110.4
C3—C5—H51104.0H91—C9—H93107.4
O6—C5—H51105.2H92—C9—H93107.6
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O8—H8···O8i0.961.762.698 (4)164
O6—H6···O6ii1.001.982.712 (4)128
O4—H4···O1iii0.981.772.718 (4)162
O1—H1···O4iv1.052.032.712 (3)120
Symmetry codes: (i) y+1/2, −x+1, z−1/4; (ii) y, −x+3/2, z+1/4; (iii) −y+3/2, x, z−1/4; (iv) −y+1, x−1/2, z+1/4.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O8—H8···O8i0.961.762.698 (4)164
O6—H6···O6ii1.001.982.712 (4)128
O4—H4···O1iii0.981.772.718 (4)162
O1—H1···O4iv1.052.032.712 (3)120
Symmetry codes: (i) y+1/2, −x+1, z−1/4; (ii) y, −x+3/2, z+1/4; (iii) −y+3/2, x, z−1/4; (iv) −y+1, x−1/2, z+1/4.
references
References top

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