CS253444B1 - Process for preparing mGtyl-3,4-O-isopropylidene-α-Lufopyranoside - Google Patents

Abstract

An improvement in the method of preparation of methyl-3,4-O-isopropylidene-α-L-fucopyranoside is achieved by condensing methyl-α-L-fulcopyranoside with anhydrous acetone at a temperature of 60 to 150°C under catalysis of 0.4 to 4 mmol. . l~i adduct of stannous chloride with pyridine in solution for 12 to 48 hours. The method of preparing methyl-3,4-O-isopropylidene-α-L-fucopyranoside is used in organic syntheses

Description

The present invention relates to a process for the preparation of methyl-3,4-O-isopropylpropyl-α-L-fucopyridine.

Methyl-3,4-O-iso-propyliidene-α-L-fucopyranoside was prepared by condensation of acetone with methyl-α-L-fucopyranoside in an anhydrous medium in the presence of alkoxides such as sulfuric acid, hydrochloric acid and desiccants such as sodium sulfate and copper sulfate. N. de Belder: Adv. Carboihydr. Chem. 20, 219 (1965)]. The reaction was carried out at a temperature of 15 to 25 ° C and (catalyst concentration (0.1 to 0.4% by weight) influenced product yield. To achieve equilibrium, the optimum catalyst concentration was determined experimentally, since in a given narrow concentration range other than It was observed that higher catalyst concentration than optimal initiated hydrolysis and also isomerization of methyl 3,4-O-isopropylidene-α-L-fucopyranoside and lower concentrations in both cases, methyl-3,4-O-isopropylidene-α-L-fucopyranoside yields were low (40-50%).

The above-mentioned disadvantages are substantially eliminated by the process for the preparation of methyl 3,4-O-isoipiropylidene-α-L-fucopyranoside by condensation with anhydrous acetone according to the invention, which is characterized in that methyl-α-L-fucopyranoside is condensed at 60 to 150 ° C. with catalysis of 0.4 to 4 mmol. . 1 ^_1 adduct of stannous chloride in pyridine in the solution for 12 to 48 hours.

The advantage of the proposed process for the preparation of methyl-3,4-O-isopropylidene-.alpha.-fuicopyranoside over the prior art is that it is simpler and more efficient, yielding a product yield of up to 89% over a wide catalyst concentration range of 0.4 to 4 mmol. 1 ^_1 . Another advantage is that they do not override the hydro, lytic and isomerization reactions, and pure methyl-3,4-O-isopropylidene, to L-fuicopyranoside, is obtained.

Example 1

To methyl-α-L-fucopyranoside (1 gj in anhydrous acetone (30 mL) was added tin (II) chloride pyridine adduct at a concentration of 0.4 mmol.l ^-1 The reaction mixture was heated in a sealed glass, nj flask at 150 ° C for After filtering, the solution is evaporated to a small volume (15 ml) at 5 kPa and shaken four times between chloroform (15 ml) and water (10 ml) to give a syrupy methyl-3,4-O- syrup. isopropylidene-.alpha.-L-fucopyranoside in a yield of 1.1 g, i.e. 89%, optical rotation [a] _D ²² -163 ° (c = 1.2, water).

Example 2

The procedure was as in Example 1 except that the reaction mixture was heated in a sealed glass flask at 110 ^° C for 24 h at 2 mmol. I ^"1 koneentrácii catalyst adduct of stannous chloride in a pyridine solution. Yield 1.1 g, i.e. 89%. Methyl 3,4-O-isopropylidene-.alpha.-L-fucopyranoside the optic, [a] _D ²² -163 ° (c = 1.2, water).

Example 3

The procedure is as in Example 1, except that the reaction mixture is heated in a sealed glass vessel at 60 ° C for 48 h at 4 mmol. 1 ^_1 koneentrácii adduct of stannous chloride in a pyridine solution. The yield was 1.0 g, i.e. 83%. Methyl 3,4-O-isopropylidene-.alpha.-L-fucopyranoside is [a] ²² _of -163 ° (c = 1.2, water).

The starting methyl-α-L-fucopyranoside for the preparation of methyl-3,4-O-isopropylidene-α-L-fucopyranoside is obtained in the following known manner [J. S. Gardiner, E. Percival: J. Chem. Soc. 1,414 (1958)]:

Example 4

L-Fucose (10 g) is dissolved in 6 wt. anhydrous methanolic hydrochloric acid] (60 ml) and the solution is refluxed under reflux, monitoring the progress of glycosidation by thin-layer chromatography on silica gel (2-butanone / water 90: 3). After reaching equilibrium (4 h), neutralize the reaction mixture with trimethylammonium methyl functional ion exchangers (Amberliet IRA-402 pract., 0.3 to

1.5 mm), filtered and evaporated at 5 kPa to a syrup. The syrup was dissolved in 2-butanone (40 mL) at 60 ° C and methyl-α-L-fucopyranoside (5.6 g, 52%) crystallized upon cooling to -5 ° C 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, .alpha.-f-fucopyranoside (2.0 g), a total yield of 7.6 g (70%). to 157 ° C and optical rotation [α] _D ^{22 -} 185 ° (c = 5.0; water).

Methyl-3,4-O-isopropylidene-α-L-fucopyra, nosid prepared according to Examples 1 to 3 is an intermediate in the preparation of methyl-2-O-methyl-α-L-fucopyranoside. It is possible to proceed in a known manner [M. Dejter-Juszynski, Η. M. Flowers: Carhohydr. Res. 28, 61 (1973)];

Example 5

To a cooled solution (5 ° C) of methyl 3,4-O-isopropylidene-α-L-fucopyranoside (1.7 g) in anhydrous 1,2-dimethoxyethane (15 ml) is added sodium hydride (0, 37 g) and the mixture was stirred at ° C for 2 h. Methyl iodide (4 ml) was then added and the reaction was monitored by thin-layer chromatography on silica gel (10: 1 v / v). After 5 h methylation was complete, water (10 ml) was added to the reaction mixture. The solution was evaporated to a small volume (15 ml) at 5 kPa and shaken four times between chloroform (15 ml) and water (10 ml). -a.-fucopyranoside (1.7 g, 94%), which is hydrolyzed with sulfo-functional ion exchangers (Amberlite IR-120 pract., 0.3 to 1.2 mm) in 50% v / v aqueous methanol (70 mL) After filtration, the solution is concentrated to 15 ml and applied onto a cob of linen silica gel 3 cm in diameter and 40 cm in length. Elution with 9: 1 by volume of chloroform and methanol yields a syrupy methyl- 2-O-methyl-α-L-fucopyranoside (1.3 g, 92%), with an optical rotation of [α] _D ²² -138.6 ° (c = 2.2; meta nol).

Methyl-3,4-O-isopropylidene -? - L-fucopyranoside can be widely used as an intermediate in the chemical synthesis of biologically active substances such as e.g. methyl-2-O-methyl-α-L-fucopyranoside, disaccharides of 2-O- (β-D-glucopyranosyl uranoic acid, β-fucose, 2-O- (α-D-galactopyranosyl uronic acid) -L-fucose. it was used to prepare methyl-2-O-methyl-α-L-fucoipyranoside - an important immunodeterminant saccharide.

Claims (1)

A process for the preparation of methyl-3,4-O-isopropylidene-N-L-fucopyranoside by condensation with anhydrous acetone, characterized in that methyl-α-L-fucopyranoside is condensed at OF THE INVENTION at a temperature of 60 to 150 ° C under catalysis of 0.4 to 4 mmol. 1 ^l of stannous chloride adduct with pyridine in solution for 12 to 48 h.