CS264167B1 - Process for the preparation of methyl 3-O-benzyl-α-L-fucopyranoside - Google Patents

Abstract

The purpose is to improve the method of preparation of methyl-3-O-benzyl-α-L-fucopyranoside. The stated purpose is achieved by benzylating methyl-α-L-fucopyranoside with three to nine equivalents of benzylbromide at a temperature of 70 to 150°C under catalysis of 0.5 to 15 mmol. 1" of stannous chloride and triethylamine as a base for 20 to 40 h. The method of preparing methyl-3-O-benzyl-α-L-fucopyranoside is used in organic syntheses as an intermediate in the preparation of biologically active di- and oligosaccharides.

Description

264167 1 2

The invention relates to a process for the preparation of methyl 3-O-benzyl-α-L-fucopyranoside.

Benzyl ethers of methyl-α-L-fulcopyranoside were prepared with benzyl [C. M. McCloskey: Adv. Carbohydr. Chem. 12, 137 (1957)] of the corresponding substituted benzyl halide derivatives in the presence of alkaline hydroxides, or later to hydride. These procedures were laborious and conspicuous, since the preparation of a suitable substituted methyl-α-L-fucopyranoside requires co-grade, often very demanding syntheses. Also, the synthesis of methyl-3-O-benzyl-α-L-fucopyranoside was complicated by the above-mentioned and, therefore, this compound was first prepared by benzylation of methyl-α-L-fucopyranoside with benzyl bromide in the presence of (bistributyltin) oxide. . Flo-wers: Carbohydr. Res. 99, 170 (1982)]. According to our finding, the preparation of meityl-3-O-benzyl-α-L-fucopyranoside by the above-mentioned compound is not sufficiently specific since a significant amount of methyl 2-O-benzyl- and methyl-4-O was formed in addition to the desired derivative. -benzyl-α-L-fucopyranosides (up to 25 and 15% w / w), which can hardly be separated from the reaction mixture. The yield of methyl-3-O-benzyl-α-L-fucopyranoside therefore does not exceed 30-35 ° / o. .

The above drawbacks are substantially hindered by the preparation of methyl-3-O-benzyl-α-L-fucopyranoside by benzylation of methyl-α-L-fucopyranoside with benzyl bromide according to the invention, in which the methyl-α-L-fucopyranoside is benzylated with three to nine equivalents of benzyl bromide at a temperature of 70 to 150 ° C under catalysis of 0.5 to 15 mmol. The preferred method of preparing methyl 3-O-benzyl-α-L-fucopyranoside by the present method is that it is more effective because it is more specific and gives up to 70%. product yield. A further advantage is that it proceeds directly from methyl-α-L-fucopyranoside, thereby eliminating the complex, time-consuming synthesis of the necessary intermediates. EXAMPLE 1 Nine equivalents of benzyl bromide (11.9 ml; 100 ml) were added to a solution of methyl α-L-fucopyranoside (2 g; 11.2 mmol) in ethyl acetate (100 ml) containing stannous chloride (190 ml; 1 mmol). 8 mmol) and triethylamine (2.3 mL; 16.6 mmol). The reaction mixture was allowed to stand in a sealed glass flask at 20 ° C for 15 h. and then heated at 110 ° C for 30 hours. Filter the cooled real wash to remove the triethylamine hydrobromide, evaporate the filtrate to a small volume (20 mL) at 5 kPa pressure, and shake four times between chloroform (20 mL) and water (10 mL). The concentrated organic layer (10 ml) was loaded onto a silica gel column with a diameter of 4 cm and a length of 60 cm. Elution with a 5: 2 mixture of chloroform and acetone gave syrupy methyl 3-O-benzyl-α-1-fucopyranoside in 2.1 g yield. j. 70%. The material has an optical duality of [α] D 22 -136.5 ° (c = 1.5; chloroform) and an analytical composition of C 62.79, H 7.66, OMe 11.70%. Calculated analytical composition for C14H20O5ίθ C 62 , 67, H 7.51, OMe 11.57%

The procedure is as in Example 1 except that the reaction mixture is heated in a sealed glass flask at 70 ° C with tree equivalents of benzyl bromide for 40 hours at 15 mmol. 11 of stannous chloride in solution. Yield 1.6 g, i.e. 53.2%. Methyl 3-O-benzyl-α-L-fucopyranoside has an optical rotation of [α] D 22 -135.2 ° (c = 1.2; chloroform) and analytical composition C 62.76, H 7.64, OMe 11.68 % .Example 3

The procedure is as in Example 1, except that the reaction mixture is heated in a quenched flask at 150 ° C with ninety equivalents of benzyl bromide for 20 hours. at 0.5 mmol. I-1 concentration of chloride chloride in solution. Yield 1.9 g, i.e. 6.13%. Methyl 3-O-benzyl-α-L-fucopyranoside optical rotation [α] D 22 -136.1 ° (c = 1.3; chloroform) and analytical composition C 62.75, H 7.66, OMe 11.68% . The starting methyl-α-L-fucopyranoside preparation of methyl 3-O-benzyl-α-L-fucopyranoside is obtained by the following known method [J. G. Gardiner, E. Percival: J. Chem. 1,414 (1958)]. Example 4 L-fucose (10 g) was dissolved in 6% by weight anhydrous methanolic hydrochloric acid (60 ml) and the solution was refluxed with a reflux condenser, followed by thin layer chromatography on silica gel in the system. 2-butanone and water 90: 3. Under equilibrium (4 hours), the reaction mixture was neutralized with functionalized trimethylammonium methyl groups (Amberlite IRA-402 pract., 0.3 to 1.5 mm), filtered, and evaporated to a syrup at 5 bar. The syrup was dissolved in 2-butanone (40 ml) at 60 ° C and then cooled to 5 ° C, where methyl-α-L-fucopyranoside (5.6 g, 52%) crystallized. (Si), the filtrate was concentrated at 5 kPaa and crystallized to give additional methyl-α-L-fucopyranoside (2.0 g). The total crystalline yield is 7.6 g, i.e. 70%. Me-

Claims (1)

264167 tyl-α-L-fucopyranoside has a melting point of155 to 157 ° C and an optical rotation of [α] D 22-185 ° [c = 5.0; water). The methyl 3-O-benzyl-α-L-fucopyranoside prepared in Examples 1 to 3 is an intermediate in the preparation of methyl 2,4-di-O-methyl-α-L-fucopyranoside. It is possible to proceed in a known manner [R. L. Whistler, J. N.BeMiller: Methods Carbohydr. Chem. 6, 376 (1972)]. Example 5 Sodium hydride (0.54 g) was added to the cooled solution (0 ° C) of methyl 3-O-benzyl-α-L-fucopyranoside (1.5 g) in anhydrous N, N-dimethylformamide (20 mL) in small portions. g) and the mixture is stirred at 20 ° C for 1 hour. Methyl iodide (2 ml) is then added sequentially and the reaction is monitored by thin layer chromatography on silica gel in a 10: 2 by volume mixture of benzene and acetone. After 3 hours, the methylation was complete, methanol (15 ml) was added to the reaction mixture, the solution was concentrated to a small volume (10 ml) at 5 kPa and shaken four times between chloroform (20 ml) and water (15 ml). ). Concentration of the organic layer gave methyl 3-O-benzyl-2,4-di-O-methyl-α-L-fulopyranoside (1.6 g, 95%) which was dissolved in methanol (40 mL). palladium catalyst (2.5 g) was added and the reaction was bubbled with hydrogen with stirring. The hydrogenolysis was followed by thin layer chromatography on silica gel in a 2: 1 mixture of benzene and acetone. After 5 h, the reaction mixture was filtered and the solution evaporated to a syrup (1 g, 93%) at 5 kPa. The syrup at 50 ° C was dissolved in methanol (25 mL) and crystallized methyl-2,4-di-O-methyl-α-L-fucopyranoside (0.6 g) by cooling to 55 ° C, which was filtered. the suction-free solution is separated on a frit (Si), the filtrate is concentrated at 5 kPa and further methyl-2,4-di-O-methyl-α-L-fucopyroside (0.3 g) is crystallized from the seed. The total crystalline yield was 0.9 g, i.e. 77.6% on the starting material. Methyl 2,4-di-O-methyl-α-L-fucopyranoside mp 79-80 ° C and optical rotation [α] D 22 -99.6 ° (c = 1.71; methanol) . The calculated analytical composition for C 9 H 18 O 5 is C 52.41, H 8.80, OMe 45.14%. Found: C 52.43, H 8.82, OMe 45.17% Methyl 3-O-benzyl-α-L-fucopyranoside has wide use as an intermediate in the chemical synthesis of biologically active di-and oligosaccharides such as 3-OaL-fulko-pyranosyl-L-fucose, O- (3-D-galactopyrano-1- (1-4) -O) - (id-D-glucopyranosyl- (1-2)] - L-fucopyranose, 0- / 3-D-glucopyranosyl uronic acid- (1-4) -O- [1,3-D-galactopyrano- zyl- (1-2)] -L-fucopyranose, O-acetyl- (1-2) -O- [SLf-pyranosyl- (1-4)] -L-fucopyranose, 2,4-di-O -acetyl-L-fucose, methyl-2,4-di-O-methyl-α-L-fucopyranoside, possibly other derivatives, in our case we have been used for the preparation of methyl 2,4-di-O-methyl- - L-fucopyranoside, an important substance in the determination of the polysaccharide and glycoprotein structure SUBJECT OF THE PREPARATION OF methyl-3-O-benzyl-α-L-fucopyranoside by benzylation of methyl-α-L-fucopyranoside with benzyl bromide, characterized in that methyl -aLf pyopyranoside is benzylated with three to nine equivalents of benzyl zinc bromide at a temperature of 70 to 150 ° C under a caustic of 0.5 to 15 mmol. 1% of tin (II) chloride and triethylamine as base for 20 to 40 hours.