2,4-Dimethyl-3,4-O-isopropyl­idene-l-arabinono-1,5-lactone

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

doi:10.1107/S160053680700476X

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 63| Part 3| March 2007| Pages o1128-o1130

https://doi.org/10.1107/S160053680700476X

2,4-Dimethyl-3,4-O-isopropylidene-L-arabinono-1,5-lactone

Kathrine V. Booth,^a ^* David J. Watkin,^b Sarah F. Jenkinson ^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 Chrystallography, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England
^*Correspondence e-mail: victoria.booth@chem.ox.ac.uk

(Received 26 January 2007; accepted 29 January 2007; online 7 February 2007)

The relative configuration at C-2 of 2,4-dimethyl-3,4-O-isopropylidene-L-arabinono lactone, C₁₀H₁₆O₅, which exists in the boat form, was unequivocally established by X-ray crystallographic analysis. The absolute configuration was determined by the use of 2-C-methyl-D-ribonolactone as a starting material.

Comment

Rare and new monosaccharides have potential both as healthy dietary alternatives (Sun et al., 2007 ; Skytte, 2002 ) and for specific chemotherapeutic uses (Nakajima et al., 2004 ; Menavuvu et al., 2006 ; Hossain et al., 2006 ). Branched 2-C-methyl pentoses have become readily available by treatment of an Amadori ketose with aqueous calcium hydroxide (Hotchkiss et al., 2007 ) and are key intermediates in the synthesis of 2-C-methyl nucleosides, a new class of drugs for the treatment of hepatitis C (Sorbera et al., 2006 ). Carbohydrates with a branch at C-2 may also be accessed by the reaction of ketoses and deoxyketoses with cyanide (Hotchkiss et al., 2004 ; Soengas et al., 2005 ). In contrast, there have been no biological studies on unprotected monosaccharides with more than one carbon branch.

The protected lactone (4) is a key intermediate in the synthesis of monosaccharides with two C-methyl branches (Booth et al., 2007 ). 2-C-Methyl-D-ribonolactone, (1), prepared by the green environmentally friendly aqueous isomerization of D-glucose (Hotchkiss et al., 2006 ), may be converted to the 3-C-methyl-L-erythronolactone (2) as previously described (Barrett & Dhanak, 1987 ; Barrett et al., 1989 ). Sequential treatment of (2) with methyl magnesium bromide followed by aqueous cyanide leads to the isolation of a major crystalline product which has a new stereogenic centre, which could be either the epimeric ribo- (3) or arabino-lactone (4). X-ray crystallographic analysis resolved the ambiguity at C-2 and unequivocally established the relative stereochemistry as the arabinono-1,5-lactone (4), which exists in a boat form; the absolute configuration of (4) is determined by the use of 2-C-methyl-D-ribonolactone (1) as the starting material.

The molecular structure of (4) is shown in Fig. 1. The molecular geometry contains no unusual features. The largest differences from the Mogul norms (Bruno et al., 2004 ) are C2—O3 (0.02 Å, Mogul s.u. 0.01 Å) and C3—C9—O8 (3.4 Å, Mogul s.u. 1.9°). The crystal structure consists of broad ribbons of hydrogen-bonded molecules lying with the plane of the ribbon perpendicular to b, and the length of the ribbon lying along a (Fig. 2). The hydrogen bonds form the backbone of the ribbon, with the individual molecules lying alternately on either side. The backbone of each ribbon lies above and parallel to the interface between two ribbons in the adjacent layers.

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.

Figure 2
Part of the hydrogen-bonded (dotted lines) ribbon lying parallel to a. The image has been rotated about c (out of the plane of the ribbon) to clarify the hydrogen-bonding chain. The molecule corresponding to the published coordinates does not form any hydrogen bonds within the natural unit cell. [Symmetry codes: (i) −x + 1, y − $[{1\over 2}]$ , −z + $[{1\over 2}]$ ; (ii) −x + $[{1\over 2}]$ , −y + 1, z + $[{1\over 2}]$ ; (iii) −x + $[{3\over 2}]$ , −y + 1, z + $[{1\over 2}]$ .]

Experimental

2,4-Dimethyl-3,4-O-isopropylidene-L-arabinono lactone (4) was crystallized from a mix of ethyl acetate and cyclohexane by vapour diffusion: m.p. 385–391 K; [α]_D²³ +131 (c, 1.5 in chloroform)

Crystal data

C₁₀H₁₆O₅
M_r = 216.23
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.3457 (2) Å
b = 12.0530 (4) Å
c = 14.1034 (5) Å
V = 1078.69 (6) Å³
Z = 4
D_x = 1.331 Mg m⁻³
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 150 K
Plate, colourless
0.40 × 0.40 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
ω scans
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.82, T_max = 0.98
6458 measured reflections
1421 independent reflections
1301 reflections with I > 2σ(I)
R_int = 0.051
θ_max = 27.5°

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.102
S = 0.86
1421 reflections
136 parameters
H-atom parameters constrained
w = 1/[σ²(F²) + (0.07P)² + 0.5P], where P = [max(F_o²,0) + 2F_c²]/3
(Δ/σ)_max < 0.001
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O8—H1⋯O7^iv	0.88	1.99	2.870 (2)	178
Symmetry code: (iv) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z]$ .

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 multi-scan process (1:1.2) reflects effects in addition to absorption, possibly connected with the flake-like aspect of the sample. 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 C 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 Å, 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.

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.

Supporting information

Crystal structure: contains datablocks global, 4. DOI: https://doi.org/10.1107/S160053680700476X/lh2305sup1.cif

Structure factors: contains datablock 4. DOI: https://doi.org/10.1107/S160053680700476X/lh23054sup2.hkl

Computing details top

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.

2,4-Dimethyl-3,4-O-isopropylidene-L-arabinono lactone top

Crystal data top

C₁₀H₁₆O₅	F(000) = 464
M_r = 216.23	D_x = 1.331 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1339 reflections
a = 6.3457 (2) Å	θ = 5–27°
b = 12.0530 (4) Å	µ = 0.11 mm⁻¹
c = 14.1034 (5) Å	T = 150 K
V = 1078.69 (6) Å³	Plate, colourless
Z = 4	0.40 × 0.40 × 0.20 mm

Data collection top

Nonius KappaCCD diffractometer	1301 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.051
ω scans	θ_max = 27.5°, θ_min = 5.3°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −8→8
T_min = 0.82, T_max = 0.98	k = −15→15
6458 measured reflections	l = −18→18
1421 independent reflections

Refinement top

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)] = 0.038	H-atom parameters constrained
wR(F²) = 0.102	w = 1/[σ²(F²) + (0.07P)² + 0.5P], where P = [max(F_o²,0) + 2F_c²]/3
S = 0.86	(Δ/σ)_max = 0.000299
1421 reflections	Δρ_max = 0.26 e Å⁻³
136 parameters	Δρ_min = −0.18 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	0.2418 (3)	0.83400 (16)	0.29155 (13)	0.0226
C2	0.1810 (3)	0.73928 (16)	0.22279 (13)	0.0215
C3	0.3015 (3)	0.74232 (16)	0.12915 (13)	0.0209
C4	0.5380 (3)	0.74540 (17)	0.15287 (14)	0.0234
O5	0.5983 (2)	0.81516 (14)	0.22116 (11)	0.0313
C6	0.4429 (4)	0.89114 (18)	0.26103 (16)	0.0299
O7	0.6698 (2)	0.68862 (15)	0.11399 (10)	0.0312
O8	0.2491 (3)	0.84518 (11)	0.08425 (10)	0.0283
C9	0.2504 (4)	0.64316 (17)	0.06758 (14)	0.0253
O10	0.2439 (2)	0.64042 (11)	0.27115 (9)	0.0235
C11	0.2262 (4)	0.66333 (16)	0.37041 (14)	0.0279
O12	0.2837 (3)	0.77729 (11)	0.37897 (9)	0.0289
C13	0.0003 (5)	0.6445 (2)	0.40394 (18)	0.0429
C14	0.3840 (5)	0.5936 (2)	0.42241 (15)	0.0407
C15	0.0713 (4)	0.92003 (18)	0.30548 (17)	0.0333
H21	0.0287	0.7394	0.2085	0.0263*
H61	0.5088	0.9295	0.3166	0.0383*
H62	0.4079	0.9467	0.2084	0.0377*
H91	0.3402	0.6474	0.0096	0.0402*
H92	0.1033	0.6442	0.0475	0.0414*
H93	0.2831	0.5762	0.1055	0.0416*
H131	−0.0088	0.6629	0.4733	0.0662*
H132	−0.0928	0.6940	0.3641	0.0656*
H133	−0.0343	0.5655	0.3920	0.0667*
H141	0.3784	0.6088	0.4914	0.0584*
H142	0.5234	0.6119	0.3969	0.0597*
H143	0.3535	0.5157	0.4100	0.0591*
H151	0.1210	0.9798	0.3445	0.0480*
H152	0.0386	0.9522	0.2446	0.0501*
H153	−0.0564	0.8859	0.3313	0.0484*
H1	0.2235	0.8363	0.0234	0.0405*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0272 (10)	0.0237 (9)	0.0169 (8)	−0.0009 (9)	−0.0020 (8)	−0.0002 (7)
C2	0.0211 (9)	0.0243 (9)	0.0189 (9)	−0.0011 (8)	0.0007 (7)	−0.0011 (7)
C3	0.0226 (9)	0.0223 (9)	0.0176 (8)	−0.0006 (8)	−0.0016 (7)	0.0009 (7)
C4	0.0242 (9)	0.0309 (10)	0.0152 (8)	−0.0017 (9)	0.0010 (8)	0.0048 (8)
O5	0.0234 (7)	0.0404 (8)	0.0301 (8)	−0.0062 (7)	−0.0002 (7)	−0.0081 (7)
C6	0.0332 (12)	0.0278 (10)	0.0287 (11)	−0.0059 (9)	0.0009 (10)	−0.0062 (9)
O7	0.0249 (7)	0.0461 (9)	0.0226 (7)	0.0056 (7)	0.0034 (6)	0.0007 (7)
O8	0.0378 (9)	0.0276 (7)	0.0195 (7)	0.0021 (7)	−0.0042 (6)	0.0031 (5)
C9	0.0280 (10)	0.0290 (9)	0.0190 (8)	−0.0017 (10)	−0.0025 (8)	−0.0035 (7)
O10	0.0317 (8)	0.0217 (6)	0.0171 (6)	−0.0023 (7)	0.0037 (6)	−0.0005 (5)
C11	0.0430 (12)	0.0232 (9)	0.0176 (9)	−0.0003 (10)	0.0063 (9)	−0.0023 (7)
O12	0.0458 (9)	0.0237 (7)	0.0172 (7)	−0.0011 (7)	−0.0037 (7)	−0.0004 (5)
C13	0.0550 (16)	0.0391 (13)	0.0345 (13)	−0.0082 (12)	0.0226 (12)	−0.0031 (11)
C14	0.0671 (18)	0.0324 (11)	0.0226 (10)	0.0087 (12)	−0.0016 (11)	0.0031 (9)
C15	0.0399 (13)	0.0294 (10)	0.0307 (11)	0.0070 (10)	0.0012 (10)	−0.0042 (9)

Geometric parameters (Å, º) top

C1—C2	1.547 (3)	C9—H91	0.998
C1—C6	1.513 (3)	C9—H92	0.975
C1—O12	1.435 (2)	C9—H93	0.990
C1—C15	1.511 (3)	O10—C11	1.431 (2)
C2—C3	1.526 (3)	C11—O12	1.426 (2)
C2—O10	1.430 (2)	C11—C13	1.526 (3)
C2—H21	0.987	C11—C14	1.499 (3)
C3—C4	1.538 (3)	C13—H131	1.005
C3—O8	1.431 (2)	C13—H132	1.010
C3—C9	1.512 (3)	C13—H133	0.992
C4—O5	1.335 (3)	C14—H141	0.991
C4—O7	1.212 (3)	C14—H142	0.980
O5—C6	1.459 (3)	C14—H143	0.974
C6—H61	1.002	C15—H151	0.960
C6—H62	1.025	C15—H152	0.965
O8—H1	0.880	C15—H153	0.979

C2—C1—C6	111.59 (16)	H91—C9—H92	107.9
C2—C1—O12	103.50 (14)	C3—C9—H93	106.8
C6—C1—O12	107.74 (17)	H91—C9—H93	111.4
C2—C1—C15	114.17 (18)	H92—C9—H93	111.6
C6—C1—C15	109.17 (17)	C2—O10—C11	106.50 (14)
O12—C1—C15	110.37 (16)	O10—C11—O12	104.39 (15)
C1—C2—C3	113.57 (16)	O10—C11—C13	110.36 (19)
C1—C2—O10	104.26 (14)	O12—C11—C13	110.94 (19)
C3—C2—O10	107.03 (15)	O10—C11—C14	108.53 (17)
C1—C2—H21	111.8	O12—C11—C14	109.1 (2)
C3—C2—H21	108.3	C13—C11—C14	113.12 (19)
O10—C2—H21	111.9	C1—O12—C11	109.79 (15)
C2—C3—C4	107.53 (16)	C11—C13—H131	108.8
C2—C3—O8	106.69 (15)	C11—C13—H132	106.8
C4—C3—O8	107.58 (16)	H131—C13—H132	112.2
C2—C3—C9	111.74 (16)	C11—C13—H133	107.3
C4—C3—C9	110.67 (17)	H131—C13—H133	111.4
O8—C3—C9	112.38 (15)	H132—C13—H133	110.1
C3—C4—O5	116.88 (18)	C11—C14—H141	110.7
C3—C4—O7	124.15 (19)	C11—C14—H142	107.3
O5—C4—O7	118.97 (19)	H141—C14—H142	110.6
C4—O5—C6	118.67 (16)	C11—C14—H143	108.6
C1—C6—O5	113.22 (16)	H141—C14—H143	110.3
C1—C6—H61	109.9	H142—C14—H143	109.3
O5—C6—H61	108.0	C1—C15—H151	110.7
C1—C6—H62	108.7	C1—C15—H152	108.3
O5—C6—H62	106.1	H151—C15—H152	106.3
H61—C6—H62	110.9	C1—C15—H153	110.7
C3—O8—H1	111.6	H151—C15—H153	111.9
C3—C9—H91	107.9	H152—C15—H153	108.8
C3—C9—H92	111.2

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O8—H1···O7ⁱ	0.88	1.99	2.870 (2)	178

Symmetry code: (i) x−1/2, −y+3/2, −z.

Acknowledgements

A generous gift of 2-C-methyl-D-ribonolactone from Novartis Pharma AG Basel is gratefully acknowledged.

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