3,4-O-Isopropyl­idene-2-C-methyl-d-galactonolactone

N Dai; S F Jenkinson; G W J Fleet; D J Watkin

doi:10.1107/S1600536810001613

. 2010 Jan 20;66(Pt 2):o406–o407. doi: 10.1107/S1600536810001613

3,4-O-Isopropylidene-2-C-methyl-d-galactonolactone

N Dai ^a, S F Jenkinson ^a,^*, G W J Fleet ^a, D J Watkin ^b

PMCID: PMC2979786 PMID: 21579826

Abstract

X-ray crystallography unequivocally confirmed the stereochemistry of the 2-C-methyl group in the title molecule, C₁₀H₁₆O₆, in which the 1,5-lactone ring exists in a boat conformation. The use of d-galactose in the synthesis determined the absolute stereochemistry. The crystal exists as O—H⋯O hydrogen-bonded layers in the ab plane, with each molecule acting as a donor and acceptor for two hydrogen bonds.

Related literature

For related literature on branched sugars, see: Booth et al. (2008 ▶, 2009 ▶); da Cruz et al. (2008 ▶); Hotchkiss et al. (2006 ▶, 2007 ▶); Jenkinson et al. (2007 ▶); Jones et al. (2007 ▶, 2008 ▶); Rao et al. (2008 ▶). For the conformations of related 1,5-lactones, see: Baird et al. (1987 ▶); Booth et al. (2007a ▶,b ▶); Bruce et al. (1990 ▶); Punzo et al. (2005 ▶, 2006 ▶).

Experimental

Crystal data

C₁₀H₁₆O₆
M _r = 232.23
Monoclinic,
a = 6.0553 (2) Å
b = 11.3612 (4) Å
c = 8.2946 (3) Å
β = 105.0854 (14)°
V = 550.97 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 150 K
0.50 × 0.40 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.91, T _max = 0.99
5558 measured reflections
1314 independent reflections
1229 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.068
S = 0.98
1313 reflections
145 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.22 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/S1600536810001613/lh2976sup1.cif

e-66-0o406-sup1.cif^{(14.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810001613/lh2976Isup2.hkl

e-66-0o406-Isup2.hkl^{(66.1KB, 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
O8—H81⋯O1ⁱ	0.81	1.99	2.771 (3)	162
O1—H11⋯O6ⁱⁱ	0.86	1.99	2.737 (3)	145

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We would like to thank the Chemical Crystallography department and ALT at Oxford University for use of the difractometers.

supplementary crystallographic information

Comment

2-C-Methyl branched sugars constitute a class of rare sugars with chemotherapeutic potential (Rao et al., 2008; Jones et al., 2008; Booth et al., 2008) as well as being chirons for the enantiospecfic synthesis of complex targets (Hotchkiss et al., 2006; Hotchkiss et al., 2007; da Cruz et al., 2008; Booth et al., 2009) including 2'-C-methyl nucleosides (Jenkinson et al., 2007). In a project to investigate the physical and biological properties of 2-C-methyl-D-galactose 4, D-galactose 1 [the use of which determines the absolute stereochemistry of the product] was converted by a number of steps to the lactols 2 (Fig. 1) (Jones et al., 2007). The reaction of 2 with sodium cyanide in water gave a chain extension to afford a single isolated crystalline product 3 (Fig. 2). 3,4-O-Isopropylidene-1,5-lactones, such as 3, invariably crystallize in a boat conformation (Baird et al., 1987; Bruce et al., 1990; Punzo et al., 2005); the diastereoselectivity may be rationalized by the formation of the galactono-lactone 3 with less steric congestion (Punzo et al., 2006; Booth et al., 2007a; Booth et al., 2007b) than in the epimeric talono-lactone. The structure of 3 is confirmed by the X-ray crystallographic analysis reported in this paper. The lactone 3 is an intermediate for the unambiguous synthesis of 2-C-methyl-D-galactose 4.

The 6-membered lactone ring adopts a boat conformation with the hydroxy group rather than the methyl group in the flagpole position (Fig. 2). The title compound exists as O—H···O hydrogen bonded layers of molecules in the ab-plane (Fig. 3, Fig. 4). Each molecule acts as a donor and acceptor for 2 hydrogen bonds. Only classical hydrogen bonds have been considered.

Experimental

The title compound was recrystallized by vapour diffusion from a mixture of ethyl acetate and cyclohexane: m.p. 423–429 K; [α]_D²⁵ +102.7 (c, 0.995 in MeOH).