CS253443B1 - Process for preparing methyl 3,4-O-isopropylidene-D-galactopyranoside - Google Patents

Abstract

Let's improve the preparation method of methyl-3,4--O-isopropylidene-α-D-galactopyranoside is achieved by condensing methyl-α-D-galactopyranoside with anhydrous acetone at a temperature of 60 to 150 °C under catalysis of 0.4 to 4 mmol. .I-1 complex of stannous chloride with pyridine in solution for 16 to 48 h. The method of preparing methyl-3,4-0-isopropylidene-α-D-galactopyranoside is used in organic syntheses.

Description

The invention relates to a process for the preparation of methyl-3,4-O-isopropylidene-α-D-galuctopyiranoside.

Methyl-3,4-O-isopropylidene-α-D-galactopyranoside was prepared by condensation of acetone with methyl-α-D-gallactopyranoside in anhydrous medium in the presence of catalysts such as hydrochloric acid, sulfuric acid and desiccants and iRo is copper sulfate and sodium sulfate [A. N. de Belder: Adv. Carhohydr. Chem. 20, 219 (1965)]. The reaction was carried out at a temperature of 15 to 25 ° C and the concentration of the catalyst (0.1 to 0.4% by weight) influenced the product yield. In order to achieve equilibrium, the optimum catalyst concentration was determined by the polysaccharide at a narrow concentration range other than optimally resulting in a reduction in the yield of methyl-3,4-O-isopropylidene-α-D-galactopyranoside. It was observed that a higher catalyst concentration than optimal initiated hydrolysis and also isomerization of methyl-3,4-O-isopropylpropylidene-α-D-galactopyranoside, and a lower concentration negatively affected the conversion of the starting methyl α-D-galactopyrainoside. In both cases, methyl-3,4-O-isopropylidene-α-D-galactopyranpidide yields were low (40-60%).

The above disadvantages are substantially eliminated by the process for the preparation of methyl-3,4-O-isopropylidene-αD-galactapyranoside by anhydrous acetone condensation according to the invention, which is characterized in that the methyl α-D-galactopyranoside is condensed at 60 to 150 ° C at catalysis of 0.3 to 4 mmol. I * ¹ with stannous chloride complex with pyridine in solution for 16 to 48 h.

The advantage of the proposed process for the preparation of methyl-3,4-O-isopropylidene-α-D-galactopyranoside over prior art processes is that it is simpler and more efficient, yielding a product yield of up to 85% over a wide catalyst concentration range of 0.4 to 4 mmol. I ^-1 . A further advantage is that no hydrolytic and isomerization reactions take place, and pure methyl-3,4-O-isopropylidene-α-D-galactopyranoside is obtained.

Example 1

Methyl-α-D-galactopyranoside (2 g) was suspended in anhydrous acetone (80 ml) and the tin (II) chloride-pyridine complex was added at a concentration of 0.4 mmol. I ^-1 . Heat the reaction mixture in a sealed glass jar at 150 ° C for 16 ih. After filtration, the solution was evaporated to a small volume (20 ml) at 5 mbar and shaken four times between chloroform (15 ml) and water (10 ml). Concentration of the organic layer yielded a syrupy product which was crystallized at 96% v / v. ethanol and petroleum ether in a total yield of 2 g, i.e. 85%. Methyl-3,4-O-isropropylidene-α-D-galactopyranoside has a melting point of 102-103 ° C, an optical rotation of [α] _D ²⁰ + 162.5 ° (c = 1.5; water).

Example 2

The procedure was as in Example 1 except that the reaction mixture was heated in a sealed glass flask at 100 ^° C for 24 h. at a concentration of the stannous chloride / pyridine complex in a solution of 2 mmol. I ¹ . The yield is 2 g, i.e. 85%. Methyl-3,4-O-isopropylidene-α-D-galactopyranoside has a melting point of 102-103 ° C, an optical rotation of [α] _D ²⁰ + 162.5 ° (c = 1.5; water). Example 3

The procedure is as in Example 1 except that the reaction mixture is heated in a sealed glass flask at 60 ° C for 48 hours. at a concentration of the stannous chloride / pyridine complex in a solution of 4 mmol. 1 ^_1 . Yield 1.9 g, i.e. 81%. Methyl-3,4-O-isopropyl-β-D-galactopyranoside has a melting point of 102-103 ° C, an optical rotation of [α] _D ²⁰ + 162.5 ° (c = 1.5; water).

The starting methyl-α-D-galactopyranoside for the preparation of methyl-3,4-O-isopropylidene-α-D-galactopyranoside is obtained as follows [J. K. Further, C.S. Hudison: J. Amer. Chem. Soc. 52, 2,534 (1930)]:

Example 4

D-galactose (10 g) was suspended in 4 wt. The reaction mixture was refluxed under reflux, monitoring the progress of glycosidation by thin layer chromatography on silica gel in chloroform / methanol (6: 1 v / v). After reaching equilibrium (15 h), the solution is neutralized with a trimethylammonium methyl functional ion exchanger (Amber Lite IRA-402 pract., 0.3-1.5 mm), filtered and evaporated at 5 kPa to a syrup. The syrup was dissolved in 2-propanol (50 mL) at 60 ^° C and, upon cooling to 0 ° C, methyl α-D-galactopyranoside monohydrate crystallized (5.7 g, 48.4%) which was separated by suction of the mother liquor on a frit. (Si), the filtrate was concentrated at 5 kPa and crystallized to give additional methyl-α-D-galactopyranoside monohydrate (1.2 g), yielding a total crystalline product of 6.9 g, ie 58.6%. at a temperature of 80 ° C and a pressure of 1.33 kPa, a crystalline methyl-α-D-galactopyranoside (6.3 g) is obtained with a melting point of 111-112 ° C, with an optical rotation of [α] D ²⁰ + 168.9 ° (c = 1.5; ethanol).

The methyl-3,4-O-isopropylidene-α-D-galacto-pyranoside prepared according to Examples 1 to 3 is an intermediate in the preparation of 2,6-di-O-methyl-D-galactose. It is possible to follow the known method [R. L. Whistler, J. N. BeMiller: Methods Carbohydr. Chem. 6, 361 (1972)]

Example 5

To a cooled solution (5 ° C) of methyl-3-, 4-O-isopropylidene, na-D-galactopyranoside (2 g) in anhydrous 1,2-dimethoxyethane (20 ml) was added sodium hydride in small portions (20 ml). 0.85 g) and the mixture was stirred at 20 ^° C for 2 h. Methyl iodine d (4 ml) was then added and the reaction was monitored by thin layer chromatography on silica gel (chloroform / acetone 9: 2). After 15 hours, methylation is complete, water (15 ml) is added to the reaction mixture, the solution is evaporated to a small volume of 15 kPa (15 ml) and shaken four times between chloroform (20 ml) and water (15 ml). methyl 3,4-O-isopropyl-2,6-di-O-meityla-D-galactopyranoside (2.1 g, 92%) was obtained, which was hydrolyzed with 5% by weight aqueous solution of hydrochloric acid. 30 ml) under a dark bulb at 100 ° C for 3 hours. The reaction mixture is neutralized with a trimethylammonium methyl functional ion exchanger (Amberlite IRA-402 wash, 0.3-1.5 mm), preG filtered and evaporated at 5 kPa. The syrup was dissolved in ethyl acetate (40 ml) at 65 ° C and 2,6-di-O-methyl-D-galactose (0.9 g, 53%) crystallized upon cooling to -5 ° C, which is separated by suction of the mother liquor on a frit (Si), the filtrate is concentrated at a pressure of 5 kPa and crystallized to give further 2,6-di-O-methyl-D-gaia The total yield of the crystalline substance is 1.4 g, i.e. 82%. 2,6-di-O-methyl-D-galactose has a melting point of 127 ^DEG -128 ^DEG C. and an optical rotation of [.alpha.] _D @ ²⁰ + 48.8 DEG for 5 min. and + 86.0 ° after 17 hours. (c = 1.25; water).

Methyl-3,4-O-isopropylidene-α-D-galactopyranoside is widely used as an intermediate in the chemical synthesis of biologically aictive di- and oligosaccharides such as 2-OaL-fucoipyranosyl-D-galactose, 6-O- (SD-galactopyranosyl- D-galactose, N-acetyl-6-O- / 3-D-glucopyranosylamine-D-galactose, 2,6-dl-O-methyl-D-galakitose, or other derivatives, in our case we used it to prepare 2, 6-di-O-methyl-O-galactose, an important substance in the determination of the polysaccharide trekking.

Claims (2)

Example 5 To a cooled solution (5 ° C) methyl-3-, 4-O-isopropylidene, na-D-galactopyranoside (2 g) in anhydrous 1,2-dimethoxyethane (20 ml) was added. Sodium hydride (0.85 g) was added in small portions and the mixture was stirred at 20 ° C for 2 hours. Iodo d (4 ml) was then added and the reaction was monitored by silica gel thin layer chromatography. chloroform / acetone 9: 2. After 15 hours complete methylation was complete, water (15 ml) was added to the reaction mixture, the solution was evaporated to a small volume (15 ml) and shaken four times between chloroform (20 ml) and water (15 ml). Concentration of the organic layer gave methyl 3,4-O-isopropyl-pylidene-2,6-di-O-methyl-D-galactopyranoside (2.1 g, 92%) which was hydrolyzed at 5% wt. aqueous solution. hydrochloric acid (30 ml) under reflux condenser at 100 ° C for 3 hours. The reaction mixture is neutralized with an ion exchanger with functional tri-methylammoniummethyl groups (Amberlite IRA-402 wash., 0.3-1.5 mm) ), filtered and evaporated at 5 kPa to syrup. The syrup was dissolved in octaneethyl (40 ml) at 65 ° C and 2,6-di-O-methyl-D- crystallized by cooling to -5 ° C. galamicose (0.9 g, 53%), which is separated by sucking off the mother liquor on a frit (Si), the filtrate is concentrated at 5 kPa and further 2,6-di-O-methyl is obtained by crystallization. -D-galactose (0.5 g). The total yield of the crystalline substance is 1.4 g, i.e. 82%. 2,6-di-O-methyl-D-galactose has a melting point of 127 to 128 CC and an optical rotation of [α] D 20 + 48.8 ° after 5 min. and + 86.0 ° for 17 hours (c = 1.25; water). Methyl 3,4-O-isopropylidene-α-D-galactopyranoside has widespread use as an intermediate in the chemical synthesis of biologically active di- and oligosaccharides, such as 2-OaL-fucicopyranosyl-D-galactose, 6-0 - (SD-galactopyranosyl-D-galactose, N-acetylated 6-O-j-D-glucopyranosylamine-D-galactose, 2,6-di-O-methyl-D-galactose, possibly other derivatives. we have used it for the preparation of 2,6-di-O-methyl-O-galactose, a useful substance in the determination of polysaccharide breakdown SUBJECT OF PREPARATION OF methyl 3,4-O-isopropylidene-α-D-galactopyranoside by condensation with anhydrous acetone, characterized in that the methyl-α-D-galactopyranoside is icondensated at 60 to 150 ° C under catalysis of 0.4 to 4 µmol / l with a complex of tin (II) chloride pyridine in solution for 16 to 48 hours.