2,3-O-Isopropyl­idene-l-apiono-1,4-lactone [(3S,4S)-3,4-dihydr­oxy-4-(hydroxy­methyl)-3,4-di-O-isopropyl­idene-4,5-dihydro­furan-2(3H)-one]

Best, D.; Jenkinson, S.F.; Watkin, D.J.; Booth, K.V.; Fleet, G.W.J.

doi:10.1107/S1600536807004230

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 63| Part 2| February 2007| Pages o1056-o1057

https://doi.org/10.1107/S1600536807004230

2,3-O-Isopropylidene-L-apiono-1,4-lactone [(3S,4S)-3,4-dihydroxy-4-(hydroxymethyl)-3,4-di-O-isopropylidene-4,5-dihydrofuran-2(3H)-one]

Daniel Best,^a Sarah F. Jenkinson,^a ^* David J. Watkin,^b Kathrine V. Booth ^a and George W. J. Fleet ^a

^aDepartment of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England, and ^bDepartment of Chemical Crystallography, Chemical Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England
^*Correspondence e-mail: sarah.jenkinson@chem.ox.ac.uk

(Received 11 January 2007; accepted 25 January 2007; online 31 January 2007)

The relative configuration of the title compound, C₈H₁₂O₅, was unequivocally established by X-ray crystallographic analysis; the absolute configuration was determined by the use of D-ribose as a starting material.

Comment

Branched 2-C-methyl nucleosides are the most promising drug candidates for the treatment of hepatitis C (Sorbera et al., 2006 ; Pierra et al., 2006 ). There is interest in the activity of nucleoside analogues with substitutents at C-3 of the sugar that may be derived from D-apiose (1D) (Sells & Nair, 1992 ; Kim et al., 2004 ). L-Nucleoside analogues – the enantiomers of the naturally occurring nucleosides – also produce novel antiviral agents (Mathé & Gosselin, 2006 ). A project to investigate nucleosides derived from L-apiose (1L) may provide chemotherapeutic leads. The title lactone, (5), is a divergent intermediate of value in the synthesis of such compounds. The crystal structure of (5) reported in this paper removes the ambiguity of the stereochemistry at C-3 of the lactone; the absolute configuration of (5) was determined by the use of D-ribose (2) as the starting material.

The isolated molecule of (5) (Fig. 1) shows no unusual features when compared with the Mogul norms (Bruno et al., 2004 ). The crystal structure consists of isolated chains of molecules linked by a single hydrogen bond, parallel to the a axis (Fig. 2). There are no hydrogen bonds between the chains, leading to crystals which were not easily cut.

Figure 1
A view of (5), with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.

Figure 2
The molecular structure of (5), along the b axis, showing the hydrogen-bonded chains lying parallel to a. There are no hydrogen bonds between the chains.

Experimental

The C-2 branched D-hamamelose, (3), prepared from D-ribose, (2) (Ho, 1979 ), was converted to the ketal of L-apiose, (4), as described previously by Yun et al. (2005 ). The lactol (4) was oxidized by bromine water (Booth et al., 2007 ) to the title compound, (5), which was crystallized from chloroform (m.p. 363 K). [α]_D²² 70 (c, 0.95 in chloroform).

Crystal data

C₈H₁₂O₅
M_r = 188.18
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.2075 (2) Å
b = 9.5645 (3) Å
c = 12.9851 (5) Å
V = 895.14 (5) Å³
Z = 4
D_x = 1.396 Mg m⁻³
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 150 K
Block, colourless
0.70 × 0.50 × 0.30 mm

Data collection

Nonius KappaCCD area-detector diffractometer
ω scans
Absorption correction: multi-scan (DENZO and SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.74, T_max = 0.97
4866 measured reflections
1171 independent reflections
1106 reflections with I > 2σ(I)
R_int = 0.035
θ_max = 27.5°

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.030
wR(F²) = 0.074
S = 0.96
1171 reflections
118 parameters
H-atom parameters constrained
w = 1/[σ²(F²) + (0.03P)² + 0.32P], where P = [max(F_o²,0) + 2F_c²]/3
(Δ/σ)_max < 0.001
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O13—H7⋯O6ⁱ	0.85	2.05	2.802 (2)	148
Symmetry code: (i) x-1, y, z.

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration assigned on the basis of the starting materials. The relatively large ratio of minimum to maximum corrections applied in the multi-scan process (1:1.51) reflects changes in the illuminated volume of the crystal. These were kept to a minimum, and were taken into account (Görbitz, 1999 ) by multi-scan interframe scaling (DENZO and SCALEPACK; Otwinowski & Minor, 1997).

The H atoms were all located in a difference map, but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry, with C—H distances in the range 0.93–0.98 Å and O—H = 0.82 Å, and with U_iso(H) = 1.2–1.5 times U_eq of the parent atom, after which the positions were refined with riding constraints.

Data collection: COLLECT (Nonius, 2001 ); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and 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

Crystal structure: contains datablocks global, 5. DOI: https://doi.org/10.1107/S1600536807004230/fl2098sup1.cif

Structure factors: contains datablock 5. DOI: https://doi.org/10.1107/S1600536807004230/fl20985sup2.hkl

Computing details top

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and 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.

(3S,4S)-3,4-dihydroxy-4-(hydroxymethyl)-3,4-di- O-isopropylidene-dihydrofuran-2(3H)-one top

Crystal data top

C₈H₁₂O₅	D_x = 1.396 Mg m⁻³
M_r = 188.18	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 1098 reflections
a = 7.2075 (2) Å	θ = 5–27°
b = 9.5645 (3) Å	µ = 0.12 mm⁻¹
c = 12.9851 (5) Å	T = 150 K
V = 895.14 (5) Å³	Block, colourless
Z = 4	0.70 × 0.50 × 0.30 mm
F(000) = 400

Data collection top

Nonius KappaCCD area-detector diffractometer	1106 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.035
ω scans	θ_max = 27.5°, θ_min = 5.1°
Absorption correction: multi-scan (DENZO and SCALEPACK; Otwinowski & Minor, 1997)	h = −9→9
T_min = 0.74, T_max = 0.97	k = −12→12
4866 measured reflections	l = −16→16
1171 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.030	H-atom parameters constrained
wR(F²) = 0.074	w = 1/[σ²(F²) + (0.03P)² + 0.32P], where P = [max(F_o²,0) + 2F_c²]/3
S = 0.96	(Δ/σ)_max = 0.000177
1171 reflections	Δρ_max = 0.21 e Å⁻³
118 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.6074 (2)	0.48960 (16)	0.48591 (12)	0.0181
C2	0.7178 (2)	0.56545 (17)	0.40266 (11)	0.0169
C3	0.9198 (2)	0.53234 (18)	0.42587 (14)	0.0241
O4	0.93534 (18)	0.45806 (14)	0.51288 (10)	0.0327
C5	0.7547 (2)	0.4199 (2)	0.55445 (13)	0.0276
O6	1.05349 (18)	0.56712 (16)	0.37647 (11)	0.0373
O7	0.65718 (17)	0.51103 (12)	0.30752 (8)	0.0206
C8	0.5685 (3)	0.37907 (17)	0.32742 (11)	0.0202
O9	0.49615 (15)	0.39187 (11)	0.42987 (8)	0.0183
C10	0.4075 (3)	0.3641 (2)	0.25376 (13)	0.0301
C11	0.7071 (3)	0.25999 (18)	0.32074 (15)	0.0322
C12	0.4786 (2)	0.58301 (18)	0.54719 (13)	0.0258
O13	0.36494 (18)	0.66645 (13)	0.48294 (11)	0.0330
H21	0.6993	0.6675	0.4071	0.0196*
H51	0.7463	0.4545	0.6261	0.0308*
H52	0.7359	0.3164	0.5507	0.0312*
H101	0.3498	0.2754	0.2701	0.0464*
H102	0.3241	0.4451	0.2678	0.0467*
H103	0.4629	0.3654	0.1853	0.0453*
H111	0.6393	0.1759	0.3427	0.0526*
H112	0.8147	0.2783	0.3660	0.0521*
H113	0.7494	0.2495	0.2485	0.0522*
H121	0.5539	0.6468	0.5897	0.0324*
H122	0.4009	0.5232	0.5952	0.0323*
H7	0.2897	0.6064	0.4591	0.0509*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0217 (8)	0.0155 (7)	0.0170 (7)	−0.0018 (6)	−0.0011 (6)	−0.0018 (6)
C2	0.0199 (7)	0.0138 (6)	0.0170 (7)	−0.0006 (6)	−0.0027 (6)	−0.0015 (6)
C3	0.0218 (8)	0.0211 (8)	0.0296 (8)	0.0001 (7)	−0.0036 (7)	−0.0023 (7)
O4	0.0260 (6)	0.0333 (7)	0.0389 (7)	0.0029 (6)	−0.0108 (6)	0.0074 (6)
C5	0.0338 (9)	0.0268 (8)	0.0222 (8)	−0.0001 (8)	−0.0058 (8)	0.0050 (7)
O6	0.0203 (6)	0.0418 (8)	0.0500 (8)	−0.0036 (6)	0.0062 (6)	−0.0015 (7)
O7	0.0305 (6)	0.0160 (5)	0.0151 (5)	−0.0079 (5)	−0.0019 (5)	0.0001 (4)
C8	0.0294 (8)	0.0154 (7)	0.0158 (7)	−0.0049 (7)	0.0025 (7)	−0.0009 (6)
O9	0.0238 (6)	0.0153 (5)	0.0159 (5)	−0.0047 (5)	0.0020 (4)	−0.0027 (5)
C10	0.0429 (11)	0.0263 (9)	0.0212 (8)	−0.0151 (9)	−0.0059 (8)	−0.0012 (7)
C11	0.0422 (10)	0.0192 (8)	0.0352 (10)	0.0014 (8)	0.0120 (9)	−0.0049 (8)
C12	0.0295 (8)	0.0236 (8)	0.0244 (8)	−0.0004 (8)	0.0040 (7)	−0.0077 (7)
O13	0.0247 (6)	0.0242 (6)	0.0501 (8)	0.0061 (5)	−0.0032 (6)	−0.0121 (6)

Geometric parameters (Å, º) top

C1—C2	1.526 (2)	C8—O9	1.4340 (18)
C1—C5	1.537 (2)	C8—C10	1.510 (2)
C1—O9	1.4303 (18)	C8—C11	1.517 (2)
C1—C12	1.514 (2)	C10—H101	0.969
C2—C3	1.520 (2)	C10—H102	0.997
C2—O7	1.4100 (18)	C10—H103	0.974
C2—H21	0.987	C11—H111	0.983
C3—O4	1.339 (2)	C11—H112	0.989
C3—O6	1.204 (2)	C11—H113	0.991
O4—C5	1.456 (2)	C12—O13	1.416 (2)
C5—H51	0.989	C12—H121	0.986
C5—H52	1.001	C12—H122	1.014
O7—C8	1.4383 (19)	O13—H7	0.848

C2—C1—C5	104.83 (13)	O9—C8—C10	108.45 (14)
C2—C1—O9	104.04 (12)	O7—C8—C11	110.83 (14)
C5—C1—O9	113.48 (13)	O9—C8—C11	110.88 (13)
C2—C1—C12	114.30 (13)	C10—C8—C11	113.47 (15)
C5—C1—C12	112.00 (13)	C8—O9—C1	108.91 (12)
O9—C1—C12	108.03 (13)	C8—C10—H101	105.9
C1—C2—C3	105.08 (13)	C8—C10—H102	105.9
C1—C2—O7	106.48 (12)	H101—C10—H102	112.4
C3—C2—O7	113.18 (14)	C8—C10—H103	105.2
C1—C2—H21	111.0	H101—C10—H103	112.8
C3—C2—H21	108.9	H102—C10—H103	113.8
O7—C2—H21	112.0	C8—C11—H111	105.7
C2—C3—O4	110.95 (14)	C8—C11—H112	110.4
C2—C3—O6	127.09 (16)	H111—C11—H112	111.3
O4—C3—O6	121.94 (16)	C8—C11—H113	109.4
C3—O4—C5	111.77 (13)	H111—C11—H113	110.1
C1—C5—O4	107.13 (13)	H112—C11—H113	109.8
C1—C5—H51	110.9	C1—C12—O13	112.18 (14)
O4—C5—H51	108.6	C1—C12—H121	108.8
C1—C5—H52	107.9	O13—C12—H121	107.4
O4—C5—H52	110.5	C1—C12—H122	109.2
H51—C5—H52	111.6	O13—C12—H122	111.1
C2—O7—C8	107.71 (11)	H121—C12—H122	108.0
O7—C8—O9	104.67 (12)	C12—O13—H7	101.7
O7—C8—C10	108.12 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O13—H7···O6ⁱ	0.85	2.05	2.802 (2)	148

Symmetry code: (i) x−1, y, z.

Acknowledgements

A generous gift of D-ribose from Dextra Laboratories Ltd, Reading, is gratefully acknowledged.

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