2,4-Di-C-methyl-α-L-arabinose mono­hydrate

In aqueous solution, the title compound, C₇H₁₄O₅·H₂O, consists of a mixture of the open-chain furan­ose and pyran­ose forms; it crystallizes solely as the α-pyran­ose form. The crystal structure exists as an extensively hydrogen-bonded network, with each mol­ecule acting as a donor and acceptor for seven hydrogen bonds. The absolute configuration of this sugar is determined by the use of 2-C-methyl-D-ribono-1,4-lactone as the starting material.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.029
• wR factor = 0.070
• Data-to-parameter ratio = 10.9

checkCIF/PLATON results

No syntax errors found



Alert level C
ABSTM02_ALERT_3_C  The ratio of expected to reported Tmax/Tmin(RR') is < 0.90
            Tmin and Tmax reported:      0.770     0.990
            Tmin(prime) and Tmax expected:      0.951     0.994
            RR(prime) =      0.813
            Please check that your absorption correction is appropriate.
PLAT061_ALERT_3_C Tmax/Tmin Range Test RR' too Large .............       0.81

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.88
           From the CIF: _reflns_number_total               1281
           Count of symmetry unique reflns         1293
           Completeness (_total/calc)             99.07%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C1     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C6     = .          R

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   5 ALERT level G = General alerts; check

   4 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Singly branched sugars have been found in nature and their occurrence has prompted interest in their synthesis and biological evaluation (Chapleur & Chrétien, 1997). For example 2-C-substituted mannose derivatives have been shown to have therapeutic potential (Mitchell et al., 2007). However, to date, no biological studies have been performed on sugars with more than one branch.

Branching of sugars can be achieved in several ways; the Kiliani reaction of ketoses with cyanide (Hotchkiss et al., 2006; Soengas et al., 2005); calcium oxide treatment of Amadori compounds (Hotchkiss et al., 2006,2007); the Aldol reaction for the introduction of hydroxymethyl branches (Ho, 1978; Koos & Mosher, 1986). Using these techniques, 2-C-methyl arabinose derivatives have been reported (Bream et al., 2006; Punzo et al., 2005). Doubly branched sugar derivatives are rare; examples include 2,4-di-C-methyl-3,4-O-isopropylidene-L-arabinono-1,5-lactone (Booth, Watkin et al. 2007) and various protected forms of 3,5-di-C-methyl-mannono and glucono lactones (Booth et al., 2007a,b,c).

Unlike the protected lactone 1 (Booth, Watkin et al. 2007), which is a twisted boat conformation, the free sugar 2 (compound numbers as in Fig. 3) can be seen to adopt the chair form (Fig. 1). The title compound exists as a three dimensionally hydrogen bonded lattice with each molecule being both a donor and an acceptor for 7 hydrogen bonds. One of the hydrogen bonds, from O13—H1, is bifurcated (Fig.2), it does however slightly exceed the normal range of hydrogen bond length.

Related literature

For related structures see: Booth, Watkin et al. (2007); Booth et al. (2007a,b,c). For background information, see: Mitchell et al. (2007); Hotchkiss et al. (2006,2007); Soengas et al. (2005); Chapleur & Chrétien, (1997); Ho (1978). For related literature, see: Booth, Best et al. (2007); Bream et al. (2006); Görbitz (1999); Koos & Mosher (1986); Punzo et al. (2005).

S2. Experimental

2,4-Di-C-methyl-3,4-O-isopropylidene-L-arabinono-1,5-lactone 1 (Fig. 3) was treated with diisobutylaluminium hydride, and deprotected with Dowex 50WX8 (H⁺) resin to give the title compound 2 (Booth, Best et al., 2007). 2,4-Di-C-methyl-α-L-arabinose 2 was crystalized from methanol by slow evaporation: m.p. 405–407 K; [α]_D¹⁷ +13 (c, 0.9 in methanol).

S3. Refinement

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

The relatively large ratio of minimum to maximum corrections applied in the multiscan process (1:1.29) reflect changes in the illuminated volume of the crystal. Changes in illuminated volume were kept to a minimum, and were taken into account (Görbitz, 1999) by the multi-scan inter-frame scaling (DENZO/SCALEPACK, Otwinowski & Minor, 1997).

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 U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Computing details

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

Figures

	Fig. 1. The title molecular structure with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
	Fig. 2. The packing of the title compound showing the extensive hydrogen bonding as dotted lines and including the bifurcated bond.
	Fig. 3. Synthesis of the title compound 2.

2,4-Di-C-methyl-α-L-arabinose monohydrate

Crystal data

C7H14O5·H2O	F(000) = 424
Mr = 196.20	Dx = 1.411 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 14290 reflections
a = 6.5700 (2) Å	θ = 5–28°
b = 9.1317 (3) Å	µ = 0.12 mm^−1
c = 15.3916 (4) Å	T = 150 K
V = 923.42 (5) Å^3	Plate, colourless
Z = 4	0.40 × 0.20 × 0.05 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1130 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.033
ω scans	θmax = 27.9°, θmin = 5.2°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −8→8
Tmin = 0.77, Tmax = 0.99	k = −11→12
16941 measured reflections	l = −20→20
1281 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.029	H-atom parameters constrained
wR(F^2) = 0.070	w = 1/[σ^2(F^2) + (0.04P)^2 + 0.05P], where P = [max(Fo^2,0) + 2Fc^2]/3
S = 0.94	(Δ/σ)max = 0.000413
1281 reflections	Δρmax = 0.21 e Å^−3
118 parameters	Δρmin = −0.19 e Å^−3
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.1831 (2)	0.70084 (17)	0.68249 (9)	0.0173
C2	0.0572 (2)	0.69771 (18)	0.76683 (10)	0.0182
C3	0.1773 (3)	0.64940 (16)	0.84777 (10)	0.0196
C4	0.3820 (3)	0.72664 (18)	0.84970 (9)	0.0234
O5	0.48881 (17)	0.71799 (13)	0.76859 (7)	0.0222
C6	0.3753 (3)	0.78939 (18)	0.70095 (9)	0.0197
O7	0.49686 (19)	0.79546 (14)	0.62744 (7)	0.0264
O8	0.21668 (19)	0.49496 (12)	0.84320 (7)	0.0220
C9	0.0617 (3)	0.68310 (19)	0.93123 (10)	0.0283
O10	−0.11528 (18)	0.60444 (12)	0.75668 (7)	0.0242
O11	0.07155 (17)	0.78427 (12)	0.61877 (7)	0.0205
C12	0.2328 (3)	0.55052 (17)	0.64519 (10)	0.0211
O13	0.7830 (2)	0.61191 (13)	0.54079 (7)	0.0308
H21	0.0112	0.8015	0.7754	0.0215*
H41	0.3582	0.8305	0.8620	0.0282*
H42	0.4683	0.6809	0.8955	0.0274*
H61	0.3449	0.8938	0.7173	0.0222*
H91	0.1445	0.6504	0.9804	0.0431*
H92	−0.0729	0.6328	0.9307	0.0421*
H93	0.0428	0.7903	0.9370	0.0427*
H121	0.3029	0.5647	0.5891	0.0336*
H122	0.1090	0.4979	0.6372	0.0331*
H123	0.3215	0.4986	0.6854	0.0327*
H4	0.1094	0.4485	0.8453	0.0343*
H5	−0.0094	0.7306	0.5930	0.0335*
H10	0.5915	0.8600	0.6343	0.0414*
H13	−0.2163	0.6588	0.7550	0.0382*
H1	0.7733	0.6409	0.4873	0.0480*
H2	0.6683	0.6463	0.5609	0.0480*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0150 (8)	0.0174 (7)	0.0195 (7)	−0.0007 (7)	−0.0003 (6)	0.0009 (6)
C2	0.0139 (8)	0.0182 (7)	0.0226 (7)	0.0018 (7)	0.0017 (6)	0.0002 (6)
C3	0.0195 (9)	0.0165 (7)	0.0228 (7)	0.0016 (7)	0.0018 (7)	0.0012 (6)
C4	0.0241 (9)	0.0251 (7)	0.0210 (7)	−0.0025 (8)	−0.0020 (7)	−0.0021 (6)
O5	0.0163 (6)	0.0261 (6)	0.0241 (6)	−0.0003 (5)	−0.0020 (5)	0.0008 (5)
C6	0.0172 (8)	0.0208 (7)	0.0211 (7)	−0.0018 (8)	0.0006 (7)	0.0011 (6)
O7	0.0221 (7)	0.0305 (6)	0.0267 (6)	−0.0084 (6)	0.0044 (5)	−0.0026 (5)
O8	0.0179 (6)	0.0165 (5)	0.0315 (6)	0.0026 (5)	−0.0010 (6)	0.0023 (4)
C9	0.0323 (10)	0.0284 (8)	0.0240 (8)	0.0071 (9)	0.0060 (8)	0.0029 (7)
O10	0.0130 (5)	0.0237 (6)	0.0358 (6)	−0.0013 (5)	0.0010 (5)	0.0034 (5)
O11	0.0193 (6)	0.0203 (5)	0.0220 (5)	−0.0017 (5)	−0.0048 (5)	0.0018 (4)
C12	0.0200 (8)	0.0191 (7)	0.0241 (7)	−0.0010 (7)	0.0021 (7)	−0.0029 (6)
O13	0.0296 (7)	0.0364 (6)	0.0264 (6)	0.0007 (7)	−0.0047 (6)	−0.0011 (5)

Geometric parameters (Å, º)

C1—C2	1.539 (2)	C6—O7	1.3861 (17)
C1—C6	1.526 (2)	C6—H61	1.006
C1—O11	1.4418 (17)	O7—H10	0.863
C1—C12	1.523 (2)	O8—H4	0.823
C2—C3	1.539 (2)	C9—H91	0.979
C2—O10	1.4261 (19)	C9—H92	0.996
C2—H21	1.003	C9—H93	0.990
C3—C4	1.519 (2)	O10—H13	0.829
C3—O8	1.4355 (18)	O11—H5	0.825
C3—C9	1.524 (2)	C12—H121	0.987
C4—O5	1.4343 (18)	C12—H122	0.952
C4—H41	0.980	C12—H123	0.974
C4—H42	0.996	O13—H1	0.867
O5—C6	1.4371 (18)	O13—H2	0.873
C2—C1—C6	107.29 (12)	C4—O5—C6	110.58 (12)
C2—C1—O11	108.09 (12)	C1—C6—O5	108.90 (12)
C6—C1—O11	105.50 (11)	C1—C6—O7	110.24 (12)
C2—C1—C12	114.59 (13)	O5—C6—O7	108.09 (13)
C6—C1—C12	111.73 (13)	C1—C6—H61	112.6
O11—C1—C12	109.20 (12)	O5—C6—H61	110.6
C1—C2—C3	114.35 (12)	O7—C6—H61	106.3
C1—C2—O10	110.21 (12)	C6—O7—H10	110.0
C3—C2—O10	108.96 (12)	C3—O8—H4	110.5
C1—C2—H21	104.8	C3—C9—H91	108.2
C3—C2—H21	108.6	C3—C9—H92	110.1
O10—C2—H21	109.8	H91—C9—H92	111.0
C2—C3—C4	109.68 (12)	C3—C9—H93	109.7
C2—C3—O8	109.53 (13)	H91—C9—H93	107.5
C4—C3—O8	107.33 (13)	H92—C9—H93	110.2
C2—C3—C9	111.63 (13)	C2—O10—H13	106.4
C4—C3—C9	109.34 (13)	C1—O11—H5	109.9
O8—C3—C9	109.23 (12)	C1—C12—H121	108.1
C3—C4—O5	113.00 (12)	C1—C12—H122	108.7
C3—C4—H41	108.2	H121—C12—H122	110.6
O5—C4—H41	107.4	C1—C12—H123	109.2
C3—C4—H42	108.9	H121—C12—H123	109.9
O5—C4—H42	108.3	H122—C12—H123	110.3
H41—C4—H42	111.1	H1—O13—H2	99.4

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O8—H4···O11^i	0.82	1.99	2.762 (2)	155
O11—H5···O13^ii	0.83	1.92	2.741 (2)	175
O7—H10···O8^iii	0.86	1.80	2.658 (2)	176
O10—H13···O5^ii	0.83	2.02	2.806 (2)	157
O13—H2···O7	0.87	2.04	2.850 (2)	153
O13—H1···O7^iv	0.87	2.37	3.065 (2)	138
O13—H1···O11^iv	0.87	2.21	2.976 (2)	147

Symmetry codes: (i) −x, y−1/2, −z+3/2; (ii) x−1, y, z; (iii) −x+1, y+1/2, −z+3/2; (iv) x+1/2, −y+3/2, −z+1.