(1S)-1,2-O-Benzyl­idene-α-d-glucurono-6,3-lactone

Sarah F Jenkinson; Daniel Best; Alexander C Weymouth-Wilson; Robert A Clarkson; George W J Fleet; David J Watkin

doi:10.1107/S1600536809002876

. 2009 Jan 31;65(Pt 2):o414–o415. doi: 10.1107/S1600536809002876

(1S)-1,2-O-Benzylidene-α-d-glucurono-6,3-lactone

Sarah F Jenkinson ^a,^*, Daniel Best ^a, Alexander C Weymouth-Wilson ^b, Robert A Clarkson ^b, George W J Fleet ^a, David J Watkin ^c

PMCID: PMC2968165 PMID: 21582005

Abstract

X-ray crystallographic analysis has established that the major product from the protection of d-glucoronolactone with benzaldehyde is (1S)-1,2-O-benzylidene-α-d-glucurono-6,3-lactone, C₁₃H₁₂O₆, rather than the R epimer. The crystal structure exists as O—H⋯O hydrogen-bonded chains of molecules lying parallel to the a axis. The absolute configuration was determined by the use of d-glucuronolactone as the starting material.

Related literature

For related literature on the synthesis of protected d-glucuronolactone, see: Sheldrick et al. (1983 ▶); Macher et al. (1979 ▶); Shah (1969 ▶). For literature related to the use of acetonide-protected d-glucuronolactone as an intermediate in the synthesis of (a) other sugars, see: Bleriot et al. (1997 ▶); Dax et al. (1991 ▶); Ke et al. (2003 ▶); Masaguer et al. (1997 ▶); (b) imino sugars, see: Dax et al. (1990 ▶); (c) sugar amino acids, see: Bashyal et al. (1986 ▶, 1987 ▶); (d) many other bioactive targets, see: Kitahara et al. (1974 ▶); Austin et al. (1987 ▶); Witty et al. (1990 ▶); Shing & Tsui (1992 ▶); Yoda et al. (2002 ▶). For the original NMR studies on benzylidene-protected glucoronolactone, see Csuk et al. (1984 ▶).

Experimental

Crystal data

C₁₃H₁₂O₆
M _r = 264.23
Monoclinic,
a = 5.6329 (1) Å
b = 7.8943 (2) Å
c = 13.3182 (3) Å
β = 99.9545 (9)°
V = 583.32 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 150 K
0.60 × 0.50 × 0.30 mm

Data collection

Nonius KappaCCD area-detector diffractometer
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.88, T _max = 0.96
8275 measured reflections
1418 independent reflections
1341 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.068
S = 0.96
1418 reflections
172 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.18 e Å⁻³

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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809002876/lh2760sup1.cif

e-65-0o414-sup1.cif^{(15.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809002876/lh2760Isup2.hkl

e-65-0o414-Isup2.hkl^{(71.3KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O7—H71⋯O1ⁱ	0.86	1.97	2.811 (3)	165

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Oxford University Crystallography Service for use of the instruments.

supplementary crystallographic information

Comment

D-Glucuronolactone 3 (Fig. 1), the only cheaply availably uronic acid, reacts with acetone in the presence of an acid catalyst to form the acetonide 4 (Sheldrick et al., 1983). With only a single unprotected hydroxyl group, the lactone 4 provides convenient access to C-5 of D-glucose and has long been used as a versatile intermediate for the synthesis of other sugars (Bleriot et al., 1997; Dax et al., 1991; Ke et al., 2003; Masaguer et al., 1997), imino sugars (Dax et al., 1990), sugar amino acids (Bashyal et al., 1986, 1987) and many other bioactive targets (Kitahara et al., 1974; Austin et al., 1987; Witty et al., 1990; Shing & Tsui, 1992; Yoda et al., 2002). Reaction of 3 with benzaldehyde in the presence of zinc chloride gives a high yield of the benzylidene protected lactones in which the epimers are formed in a ratio of approximately 5:1 (Macher et al., 1979; Shah, 1969). The configuration of the benzylidene acetal has previously been investigated by NMR experiments which suggest that 1, which is the major product, has the 1,2(S)-configuration (Csuk et al., 1984). The crystallographic analysis confirms that this assignment is correct and that the major product is 1. Although as yet there have been no examples of the use of the benzylidene acetals 1 and 2 as synthetic intermediates, it is likely there will be cases where the use of a benzylidene group, which can be removed by hydrogenation, will have a significant advantage over the acetonide 4, where strong acid must be used to remove the protecting group.

The title compound (Fig. 2) exists as alternating layers of hydrogen bonded chains of molecules lying parallel to the a-axis (Fig. 3, Fig. 4). Only classical hydrogen bonding has been considered. The absolute configuration was determined by the use of D-glucuronolactone as the starting material.

Experimental

The title compound was recrystallized by vapour diffusion from a mixture of ethyl acetate and cyclohexane: m.p. 419.5–421.5 K; [α]_D²⁰ +67 (c, 1.0 in acetone) (Macher et al., 1979).