Synthesis and Molecular Structure of Methyl 4-O-methyl-α-D-glucopyranuronate

A method for the preparation of methyl 4-O-methyl-α-D-glucopyranuronate and its single crystal X-ray structure determination are reported. The molecule adopts an almost ideal 4C1 (OC3) conformation.


Introduction
(4-O-Methylglucurono)xylans are important constituents of cell-wall polysaccharides of woods and other plants. These biopolymers are composed mainly of (1→4)-β-linked D-xylopyranoses, some of which are randomly branched at position O-2 with 4-O-methyl-α-D-glucopyranosyluronic acid. In this respect, methyl (benzyl 2,3-di-O-benzyl-4-O-methyl-β-D-glucopyranosid)uronate (1) and methyl 4-O-methyl-α-D-glucopyranuronate (2) represent very useful compounds in the synthesis and structural studies of model aldobiouronic acids (needed in studies related to chemical processing of wood) that reflect these structural features [1][2][3][4]. Regarding the preparation of 2, there are two methods described in the literature. The first is based on the conversion of 4-O-methyl-D-glucuronic acid to the corresponding methyl ester by refluxing in absolute methanol in the presence of Dowex-50 X-8 (H + ) resin for 20 h [5]. The product was used in the next reaction step without isolation and neither experimental nor structural description data were given. The second method involves the deacetylation of methyl 1,1,2,3,5-penta-O-acetyl-4-O-methyl-aldehydo-D-glucuronate affording methyl 4-O-methyl-D-glucopyranuronate as an unseparable mixture of α-and β-anomers and, therefore, only uncomplete 1 H-NMR data, [α] D and R f values were given for this mixture [6]. Pure α-anomer was incompletely characterized ( 1 H-NMR, [α] D , R f ) only as a corresponding 1,2,3-tri-O-acetyl derivative [6]. We now report an alternative method for the preparation and isolation of a single anomer -methyl 4-O-methylα-D-glucopyranuronate (2) as well as its relevant structural and spectral characteristics, including Xray crystallography data.

Results and Discussion
According to published results [7], acetolysis of (1) led to the formation of both α-and β-1-Oacetates. On the other hand, acid hydrolysis of benzyl 2,3-di-O-benzyl-4-O-methyl-β-D-glucopyranosiduronic acid produced the 1-O-deprotected derivative which, without isolation, was treated with diazomethane to give the corresponding methyl glucopyranuronate as a single α-anomer [7]. It is evident that anomerization must occur during both mentioned reactions. In our hands, conventional debenzylation (hydrogenation, Pd/C) of the known 1 [7] afforded an about 2:1 mixture (by NMR) of αand β-anomers of methyl 4-O-methyl-D-glucopyranuronate, from which the title α-anomer 2 was isolated by the slow crystallization using acetone as a solvent (Scheme 1). The relevant coupling constant J 1,2 = 3.6 Hz in the 1 H-NMR as well as the signal at 93.2 ppm in the 13 C-NMR spectrum, respectively, are indicative of an α-configuration at the anomeric position in 2.
This structural arrangement was unambiguously confirmed by X-ray crystalography. A perspective view and the numbering scheme adopted for the molecule of 2 is depicted in Figure 1. The selected bond lengths and bond angles are listed in Table 1. A list of selected torsion angles is given in Table 2. The hydrogen bond geometry is shown in Table 3. The relevant crystallographic and structure refinement data for glucopyranuronate 2 are given in Table 4. Atomic coordinates and displacement parameters have been deposited with CCDC as supplementary information [8].
Due to absence of such protecting groups which could impose some conformational rigidity on molecule of 2, it is not surprising that the values of the relevant torsion angles O5-C1-C2-C3 = 60.05 (13)       Analysis of the molecular packing in the unit cell revealed six principal hydrogen bonds (Table 3 and Figure 2). The first-level descriptors based on the graph-set theory [10] [10] was obtained using the program PLUTO [11]. For convenience, the Xa,d(n) notation has also been adopted in this paper, in which (X) is the pattern descriptor, (a) is number of acceptors, (d) is number of donors and (n) is the number of atoms comprising the pattern.

Figure 2.
Hydrogen bonding pattern in compound 2. For notation and symmetry codes see Table 3.

X-ray techniques
X-ray quality crystals of the title compound 2 were obtained by slow crystallization from dilute acetone solution. Crystal and experimental data are summarized in Table 4. Preliminary orientation matrix was obtained from the first frames using Siemens SMART software [12]. Final cell parameters were obtained by refinement of 6468 reflections using Siemens SAINT software [12]. The data were empirically corrected for absorption and other effects using the SADABS program [13] based on the method of Blessing [14]. The structure was solved by direct methods and refined by full-matrix leastsquares on all F 2 data using Bruker SHELXTL [15]. The non-H atoms were refined anisotropically. Hydrogen atoms were constrained to the ideal geometry using an appropriate riding model. Molecular graphics were obtained using the program DIAMOND [16].