CS225170B1 - Preparation of methyl-alpha-d-mannopyranoside - Google Patents

Description

It is an object of the present invention to provide a method for preparing methyl-α-D-manopyranoside by glycosidizing a mixture of D-glucose and D-mannose obtained by epimerizing D-glucose.

The preparation of methyl-α-D-mannoside from pure D-mannose using the Fischer glycosidation method does not present any difficulties. In the presence of higher concentrations of mineral acids in methanol and a higher reaction temperature (0.25% HCl, reflux) methyl-α-D-manopyranoside is obtained (E. Fischer, L. Beensch; Ber. 29, 2927 (1896)), when milder. Reaction conditions (cation exchange catalysis yields a 1: 1 mixture of methyl-α-D-manopyranoside and methyl-α-D-manofuranoside in the presence of smaller amounts of β-anomeric forms (DF Mowery Jr., Methods in Carbohydrate Chemistry, Vol. II.) p. 328, Academic Press Inc, New York-London, 1963. The interconversion of the isomeric forms of methyl-D-mannoside already takes place under very mild reaction conditions (0.01 and 0.1% HCl in methanol, 35 ° C, respectively). C) and in each case the α-anomers of methyl-D-mannoside are preferred (V. Smirnygin, CT Bishop; Can. J. Chem. 46, 3085 (1968)) .The proposed method of preparation utilizes reaction conditions conditional on the preferred formation of methyl-α-D- manopyranoside and at the same time utilizes its particularly good crystal 2 the ability of the leaching of alcoholic or aqueous-alcoholic solutions, respectively. The starting D-mannose for glycosidation is provided by the epimerization of D-glucose catalyzed by molybdenum ions (V. Bilik: Chem. Rumor 26, 187 (1972)).

SUMMARY OF THE INVENTION In a slightly acidic aqueous solution, D-glucose is epimerized under the catalytic action of molybdenum ions to form an equilibrium mixture of D-glucose and D-mannose, from which a portion of D-glucose is recovered by crystallization and D- mannose is converted to methyl-α-D-manopyranoside by acid-catalyzed glycosidation with methanol. From the glycosidation mixture, methyl-α-D-manopyranoside is obtained directly by crystallization in 14% yields, calculated on the starting D-glucose and d-glucose, respectively. 28% yields based on the reclaimed portion of D-glucose by crystallization.

An advantage of the proposed process for the preparation of methyl-α-D-manopyranoside is that - prior to the epimerization reaction, D-glucose, which is substantially more accessible than D-mannose, is actually used. crystallization mother liquors from which it is no longer possible to obtain further amounts of crystalline D-mannose,

225176 - is low on technological equipment and - the necessary chemicals are commonly available.

Example 1

A mixture of D-glucose (300 g), water (1500 ml) and molybdic acid (3 gj) is heated at 90-95 ° C for 4 h. The solution is then concentrated and the syrup-like residue is dissolved in methanol: ethanol 1: 1 ( 400 ml) and allowed to crystallize at room temperature for 18 to 20 h to regenerate a portion of D-glucose (150 to 180 g), concentrate the mother liquor to dryness, dissolve the residue in methanol (1000 ml) and add dimethylsulfate ( 10 mL) was heated at 65 ° C for 8 h. The solution was then discarded and allowed to crystallize at room temperature for 18-20 h to give a first portion of methyl-α-D-manopyranoside (32 g) o [α] _D ²³ + 80 ° + 1 ° (c 1, water) After concentrating the mother liquor to 1/3 volume, a second portion of methyl-α-D-manopyranoside (14 g) crystallized by [α] _D ²³ + 78 ° + 0.5 ° (c 1 , Water).

Example 2

A mixture of D-mannose (100 g), methanol (1000 mL) and dimethyl sulfate (10 mL) was heated at 65 ° C for 8 h and then allowed to stand at room temperature for 18-20 h. A crystalline portion of methyl-α-D-manopyranoside (89 g) is filtered off, another portion of D-mannose (100 g) is dissolved in the filtrate and the solution is adjusted to a flood volume (to 1000 to 1100 ml) by adding methanol. the crystallization procedure is repeated as described above to give a second portion of methyl-α-D-manopyranoside (87 g), and a second cycle of glycosidally repeated with the addition of another portion of D-mannose (100 g) to give a third portion of methyl-α-D- Finally, the filtrate is neutralized by the addition of powdered barium carbonate, and after concentration of the filtrate (to about 300 ml volume), a fourth crop of methyl-α-D-manopyranoside (27 gj) is obtained. The total yield of crystalline methyl-α-D-manopyranoside is 89.1 ® / o.

recrystallization

Methyl-α-D-manopyranoside (100 g) is dissolved in water (100 ml), purified with charcoal, then thickened methanol (400 ml) is added to the filtrate and the solution is allowed to stand at room temperature for 5 hours to give methyl-aD. -manopyranoside, mp 191 ° C and [α] ²³ + 77.5 ° ± 0.5 ° (c 1, water) Literature (DF Mowery Jr., Methods in Carbohydrate Chemistry, Vol. II p. 328, Academie Press, Inc., New York - London, 1963) gives the methyl-a-D-mannopyranoside mp 190-192 ° C, (a] D ²⁰ L-78 ° (c 2, water), respectively. (E. Fischer, L. Berens 29 2927 (1898) mp 193-194 ° C and [α] D + 79.2 ° (water).

The invention chemically evaluates D-mannose to a commercially interesting derivative - methyl-α-D-manopyranoside.

Claims (1)

2 2 5 1 7 fl - low on technological equipment and - the necessary chemicals are commonly available. Example 1 A mixture of D-glucose (300 g), water (1500 ml) and molybdic acid (3 g) was heated to 90-95 ° C for 4 h. The solution was then concentrated and the syrup residue dissolved in methanol-ethanol 1: 1 (400 mL) and crystallized at room temperature for 18-20 h to regenerate a portion of D-glucose (150-180 g). The mother liquor is concentrated to dryness, the residue is dissolved in methanol (1000 ml) and, after addition of dimethyl sulphate (10 ml), the mixture is heated at 65 ° C for 8 h. The solution is then discarded and allowed to crystallize for 18-20 h. to obtain the first portion of methyl α-D-mannopyranoside (32 g) of [α] D 23 + 80 ° + 1 ° (c 1, water). After concentration of the mother liquor to 1/3, the second portion of methyl .alpha.-D-mannopyranoside (14 g) was crystallized by [.alpha.] D @ 23 + 78 DEG + 0.5 DEG (c 1, water). Example 2 A mixture of D-mannose (100 g), methanol (1000 ml) and dimethyl sulfate (10 ml) was heated at 65 ° C for 8 h and then the solution was allowed to stand at room temperature for 18-20 h. The manopyranoside (89 g) is filtered off, another portion of D-mannose (100 g) is dissolved in the filtrate and the solution is adjusted to the flood volume by adding methanol (per 1000 to 1100 ml). The thus prepared reaction mixture is refluxed for 8 h and the crystallization process is repeated as described above to give a second crop of methyl α-D-mannopyrazide (87 g). The second cycle of glycosidation was repeated with the addition of a further portion of D-mannose (100 g) to give a third portion of methyl-α-D-mannopyranoside (85 g). Finally, the filtrate is neutralized by the addition of barium carbonate powder and, after concentration of the filtrate (to about 300 ml volume), a fourth portion of methyl-α-D-mannopyranoside (27 g) is obtained. O. Recrystallization Methyl-α-D-mannopyranoside (100 g) was dissolved in water (100 mL), purified with charcoal, then methanol (400 mL) was added to the filtrate and the solution allowed to stand at 5 ° C for more hours to yield methyl. -α-D-mannopyranoside tt 191 ° Ca (d) d 23 + 77.5 ° ± 0.5 ° (c 1, water). Liturgy (DF Mowery Jr.; Methods in Carbohydrate Chemistry, Vol. II. P. 328, AcademiePress Inc., New York-London 1963) reports mp 190-192 ° C for methyl-α-D-mannopyranoside and ( a] D 2 O-1 78 ° (c 2, water) respectively (E. Fisher, L. Beensch; Ber 29 2927/1898) mp 193-194 ° C and [α] D + 79.2 ° ( The invention chemically enhances D-mannose by a commercially interesting derivative of methyl-α-D-mannopyranoside, the object of which is the preparation of methyFa-D-mannopyranoside by treatment with D-mannose conversion methanol, characterized in that epimers to methyl-α-D-mannopyranoside, which is destroyed by catalytic action of molybdenum-isolates from the glycosidation mixture of directly crystalline ions, and from the resulting mixture by D-glucose zy and D-mannose.