SU447886A1 - The method of obtaining protected 4,6-0-alkylidene - - -glucopyranose - Google Patents

Description

(54) METHOD FOR OBTAINING PROTECTED 4,6-O-ALKYLIDENE-. Glucopyranose R / GO o o. O4-o-c. Where C has the indicated value, which is then reacted with acetic anhydride or formic acetic anhydride, usually with pyridine, acetylated by reaction with activated acetic acid derivatives, usually in the presence of pyridine or formulated and the compound thus obtained with the general formula 4 t5 O 0-C-0-CH2 20 J / ps4 / where C and I have the indicated values, is subjected to catalytic hydrogenation in the presence of palladium, followed by separation of the products in a known manner. Only palladium, freshly prepared by reduction of palladium chloride, is suitable for hydrogenolytic cleavage of the benzyloxycarbonyl group. When this hydrogenolysis is carried out in a dry solvent that does not contain hydroxyl groups, preferably in acetone. The compound of formula 2 used as the starting material is obtained by reacting an aliphatic aldehyde with glucose in the presence of an acidic catalyst. ..., Example 1. 4,6-O-ethylidene-2,3-di-0-acetyl-J) -glucopyranose. A, Sodium salt 4,6-O-ethylidene-D-glucopyranose. 41.6 g of 4,6-0-ethylidene-D -glucopyranose are added to 102 ml of 2-n sodium hydroxide solution, cooled to 0 ° C, and stirred to dissolve. Then 10OO ml of ethanol / ether mixture (3 ;; 2) are poured, stirred for 15 minutes while cooling, the ice is filtered off from the precipitate, washed with 20O ml / ethanol, then ZOO ml. ether and dried in high vacuum at room temperature, get the sodium salt of 4,6-0-ethylidene-1-glucopyranose. B. 4,6-ethylidene-1-0-benzyloxycarbonyl- - D -glucopyranose. To a suspension of 4O g of sodium salt of 4,6-Oethylidene-D-glucopyranose in 750 ml of absolute alcohol-free chloroform was added 4O g, 75% strength chloroformate benobyl ether and stirred for 16 hours in the absence of moisture at 20 ° C. Then 16O ml of isopropanol is added, it is stirred for 5 minutes, 200 ml of chloroform / isopropanol (4: 1) is added and washed 3 times with water (1OO ml). After drying over sodium sulfate, the organic phase is evaporated in a vacuum and the residue; -. extracted 3 times with ether (150 ml each) The insoluble residue is dissolved in 900 ml of hot ethyl acetate, concentrated in a weak vacuum to 30%, after which crystallization begins. The 4,6-0-ethylidene-1-O-benzyloxycarbopyl-D-glucopyranose is obtained, which, after recrystallization from ethyl acetate, melts at 168-169 ° C (needles); о.- 27.7 ° (with 1.044, chloroform). B. 4,6-0-ethylidene-1-0-benzyloxycarbonyl-2, 3-di-0-acetyl- - D -glucopyranose. To a mixture of 50 ml of absolute pyridine and 5O ml of acetic anhydride, 42.5 g of 4,6-O-ethylidene-1-O-benzyloxycarbonyl-J) -glucopyranose were added and incubated for 15 hours, first with cold water and then at 20 ° C. Then the reaction solution is evaporated in vacuo, the residue is dissolved 3 times in benzene (1OO ml each), the benzene is evaporated in vacuum and the residue is recrystallized from 1OO ml of acetone, added 30 ml of ether. After recrystallization from acetone / ether / pentane, 4,6-O-ethylidene-1-O-benzyloxycarbonyl-2, 3-di-0-acetyl- is obtained. - D -glucopyranose, so pl. 161 ° C; - 41.6 ° (from 0.954 chloroform). G. 4,6-0-ethylidene-2,3-di-0-acetyl-3 - D -glucopyranose. 50 mg of Pd C1 is dissolved in 50 ml of water and, by adding 10 ml of methanol, hydrogenated for 1 hour at 2 ° C and atmospheric pressure. After that, the upper layer of the solution is decanted from the precipitated metal palladium, washed thoroughly, freeing the palladium from the acid, and the methanol is removed by washing three times with dry acetone in 15O ml. The palladium catalyst thus obtained is suspended in 25 O of dry acetone, 25.5 g of 4,6-.0-ethylidene-1-0-benzyl, hydroxycarbonyl-2,3-di-O-acetyl-y8 - J5 - are added. glucopyranose and hydrogenated for j 1 hour at 20 ° C and atmospheric pressure. After filtering the catalyst, it is washed with 100 ml of dry acetone, the filtrate is evaporated in vacuo at 35 ° C (bath temperature) and the residue is dried for 1 hour at 30 min under high vacuum. For crystallization, 50 ml of diisopropyl ether with a temperature of 35–30 ° C are poured over it. From acetone / pentane, 4,6-0-ethylidene-2,3-di-.0-.acetyl-3-D -glucopyranose crystallizes, t. square 109–111 ° C; WD - 35.9 ° (c 1.006, chloroform P. M and R 2. 4,6-O-ethylidene-2,3-di-0-formyl- / i - D-glucopyranose. A. 4,6 -0-ethylidene-1-0-benzyloxycarbonyl-2, 3-di-0-formyl-8-D-glucopyranose "25.5 g of 4,6-0-ethylidene-1-.0-benzyloxycarbonyl-jB-T) α-glucopyranose suspended in 2OO ml of absolute methylene chloride. The suspension is cooled to -20 ° C and, by adding 86 ml of formioacetic an-1-idrid, stirring for 10 minutes at. After that, a solution of 6O ml of absolute pyridine in 100 ml of absolute methylene chloride is added dropwise over 45 minutes with stirring without access of moisture and at an internal temperature of 20 ° C. 5 minutes after the end of the addition of pyridine, the mass is diluted with 200 ml of methylene chloride, washed 4 times 250 ml of water and evaporated the organic phase, dried over sodium sulfate, in vacuo, the oily residue is evaporated 4 times with benzene (1OO ml) in vacuo and then dried in vacuum at 60 C. Using crystallization from 70 ml acetone, added 30 ml ml This gives a slightly colored crystallized solution, which is dissolved in 100 ml of acetone and purified with the help of 1 g of active charcoal. After filtering off the carbon, the solution is concentrated in vacuo to approximately 60 ml and, after adding 50 ml of dry ether, is subjected to crystallization. Analytical 4,6-0-ethylidene-1-0-benzyloxycarbonyl-2, 3-di-O-formyl-D - D-gluconyranose is melted at 125-126 ° C; Of -38.2 (with 1.022 chloroform).

Formic acid anhydride. To 48 ml of acetic anhydride is added dropwise with stirring without access of moisture and cooling with ice, 38 ml of anhydrous mussel acid for 2O-30 min. P) In this, the internal temperature should not exceed 25 ° C. The mixture is left standing

where C has the specified value

converted into sodium salt by means of sodium hydroxide solution, the resulting sodium eO salt is reacted with chloroformate benobyl ether to give compounds of the general formula 4 hours at 20 C. The anhydride obtained in this way is used for the formylation, B. 4,6-0-ethylidene -2,3-di-O-formyl-j3 - D -glucopyranose. As described in Example 1, from 24.0 g of 4,6-O-ethylidene-1-O-benzyloxycarbonyl--2,3-di-O-formyl-jS-D -glucopyranose with the same amount of palladium catalyst, after hydrogenation, a crude 4,6-O-ethylidene-2,3-di-O-formcle- - jQ - J3 -glucopyranose, crystallization from dry acetone / ether / pentane and two times from dry acetone / ether form pure crystals for analysis. m.p. 109-114 C / 135-137 °; 37.9 ° (c. 1.052, chloroform). The subject of the invention is 1. A method for producing a protected 4,6 0-alkylidene-j3 - D -glucopyranose of the general formula where is an alkyl group with 1-5 carbon atoms; - a formyl or acetyl group, characterized in that 4,6-O-alkylidene glucopyranose of the general formula

about

HE

R

where (. has the indicated value,

which is acetylated or formylated, the compound of the general formula thus obtained

where and C, have the indicated meanings,

subjected to catalytic hydrogenolysis in the presence of palladium in a dry solvent that does not contain hydroxyl

groups, with the use of products in a known manner.

2. The method according to p. 1, characterized in that as a dry solvent, not containing hydroxyl, use acetone.