CN102093439A - Preparation method of 2-O-ethoxyl-D-glucose - Google Patents
Preparation method of 2-O-ethoxyl-D-glucose Download PDFInfo
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Abstract
The invention provides a preparation method of 2-O-ethoxyl-D-glucose, belonging to the technical field of chemical synthesis. The method comprises the following steps of: carrying out glucoside treatment on merchant D-glucose, and protecting 4,6-site hydroxyl groups with benzaldehyde; and then selectively carrying out nucleophilic substitution and hydrolysis with 2-bromoethanol pyran ether to synthesize the 2-O-ethoxyl-D-glucose. The method has the advantages of low cost and easiness of obtaining raw materials, moderate reaction condition, fewer synthesis steps, high productivity, convenience for operation, and the like.
Description
Technical field
The invention belongs to chemosynthesis technical field, relate to a kind of saccharide compound, relate in particular to saccharide compound that a kind of very important hydroxyethyl replaces and preparation method thereof.
Background technology
EPO is the abbreviation of erythropoietin (Erythropoietin), is by a kind of hormonelike material of kidney and hepatic secretion, can promote red blood cell proliferation, increases that oxygen generates in the muscle, thus make muscle energeticallyer, the working hour is longer.After this people utilize that gene recombination technology is synthetic have been generated recombinant human erythropoietin (rhEPO) and be used for the treatment of anaemia.But a lot of sportsmen find that but rhEPO causes abuse to sports achievement raising effect, and user's health is caused serious harm.For this reason, IOC Medical Comm. in 1989 formally classifies EPO as forbidden drugs.In order to escape detection, some sportsmen uses its sequestering agent again after using EPO---and hydroxyethylamyle (Hydroxyethyl Starch, HES).It is as being blood swelling agent use that hydroxyethylamyle begins, many afterwards countries with it as blood substitute.In the forbidden drugs table is listed HES in January, 2000 by the International Olympic Committee.
2-O-hydroxyethyl-D-glucose is the acidic hydrolysis product of hydroxyethylamyle, and the hydroxyethyl glucose in monitoring sportsmen's blood or the urine acidic hydrolysis thing can infer rapidly and accurately whether the sportsmen takes these type of prohibited items, so as standard reagent.
The structure of 2-O-hydroxyethyl-D-glucose is shown below:
The synthetic method of 2-O-hydroxyethyl-D-glucose has multiple, and it all is at first that glucose is synthetic with Paraformaldehyde 96 under acidic conditions that these method summaries get up.But these methods on the whole, and productive rate is very low, and operational path is long, complicated operation, cost height.
Summary of the invention
The objective of the invention is in order to overcome problems of the prior art, provide a kind of environment-protecting asepsis, yield height, cost is low, synthetic route is short, the method for simple and direct effective Synthetic 2-O-hydroxyethyl-D-glucose.
The present invention prepares the method for 2-O-hydroxyethyl-D-glucose, comprises following processing step:
(1) preparation of α-Pu Taotang first glycosides: alpha-D-glucose is joined in the methanol solution of hydrogenchloride, be heated to 65 ~ 70 ℃ of back flow reaction 48 ~ 72 hours, cooling, underpressure distillation, crystallisation by cooling, suction filtration, Air drying obtains the white powder solid.
In the methanol solution of described hydrogenchloride, the mass percent of hydrogenchloride is 7% ~ 15%; The mole number of methyl alcohol is 16 ~ 17 times of alpha-D-glucose.
(2) 4, the preparation of 6-O-benzal-alpha-D-glucose first glycosides: with the tosic acid is catalyzer, in non-proton organic solvent, with α-Pu Taotang first glycosides and 2, the 2-dimethoxy-p is with the mixed in molar ratio of 1:1 ~ 1:1.5, in 65 ± 5 ℃ of reactions 1 ~ 2 hour of reducing pressure down, the pressure reducing and steaming solvent is used the sodium bicarbonate aqueous solution crystallization, suction filtration, Air drying obtains 4,6-O-benzal-alpha-D-glucose first glycosides.
Described non-proton organic solvent is N, dinethylformamide, 1,4-dioxane, tetrahydrofuran (THF), pyridine.
(3) 4, the preparation of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides: in non-proton organic solvent, earlier with 4,6-O-benzal-alpha-D-glucose first glycosides, sodium hydride is with the mixed in molar ratio of 1:1.2 ~ 1:1.8, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-1.2 ~ 1.5 times of amounts of alpha-D-glucose first glycosides molar weight, 45 ~ 60 ℃ of down reactions 6 ~ 12 hours, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying, filter, the pressure reducing and steaming solvent, column chromatography for separation obtains product;
Described non-proton organic solvent is N, dinethylformamide, 1,4-dioxane, tetrahydrofuran (THF), pyridine.
(4) preparation of 2-O-hydroxyethyl-D-glucose: with 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides with the dilute hydrochloric acid of 0.5 ~ 1mol/L 95 ~ 100 ℃ of following hydrolysis 8 ~ 12 hours, the pH value of sodium hydroxide solution adjusting mixing solutions is 6.5 ~ 7 again, underpressure distillation boils off solvent, use methanol extraction, anhydrous magnesium sulfate drying filters, the pressure reducing and steaming solvent, column chromatography for separation obtains product.
Step (4) is described 4, and the quality-volume ratio of the dilute hydrochloric acid of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 0.5 ~ 1mol/L is 1g:25ml ~ 1g:40ml.
Its synthetic route is as follows:
2-O-hydroxyethyl-D-the glucose of the present invention's preparation, the detection through detection meanss such as NMR (Nuclear Magnetic Resonance) spectrum, infrared spectra, mass spectrum, X-single crystal diffractions shows that its structure is consistent with re-set target, proves that the synthetic of this important compound is successful.
The present invention utilizes commercially available D-glucose after twice protection of perhydroxyl radical, through hydrolysis one-step synthesis 2-O-hydroxyethyl-D-glucose, has advantages such as raw material is cheap and easy to get, reaction conditions is gentle, productive rate is high, easy to operate.
Embodiment
Be described further below by of the preparation of concrete experimental example 2-O-hydroxyethyl of the present invention-D-glucose.
Embodiment 1
(1) preparation of α-Pu Taotang first glycosides
The exsiccant hydrogen chloride gas is passed in the 200g absolute methanol solution, treats that its quality increase stops during 16g at least; Then the hydrogen chloride methanol solution that makes is diluted to 1800ml, adds anhydrous D-glucose 500g again, reaction is 72 hours under the reflux, cooling, underpressure distillation goes out most of solvent, crystallisation by cooling, suction filtration, Air drying obtains white powder solid (266g), and its productive rate is 49.5%.
The preparation of (2) 4,6-O-benzal-alpha-D-glucose first glycosides
In the single port flask of 1000ml, add 400ml N successively, dinethylformamide, α-Pu Taotang first glycosides (100g) and 2,2-dimethoxy-p (76g), tosic acid (2.5g) in 65 ± 5 ℃ of reactions 2 hours of reducing pressure down, is warming up to 100 ℃ of pressure reducing and steaming solvents, add sodium bicarbonate aqueous solution (2%) 50ml again after being cooled to room temperature, place crystallization, suction filtration, Air drying, obtain the white powder solid and be 4,6-O-benzal-alpha-D-glucose first glycosides.Yield is 58%.
Above-mentioned synthetic 4,6-O-benzal-alpha-D-glucose first glycosides, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(CDCl
3,?400?MHz)，δ?(ppm):7.46-7.33?(m,?5H),?5.51?(s,?1H),?4.76?(d,?
J?=3.9Hz,?1H),?4.26?(m,?1H),?3.9?(dd,?
J?=9.3?9.3Hz,?1H),?3.74-3.71?(m,?2H),?3.60?(dd,?
J?=3.9?9.3Hz,?1H),?3.46?(t,?
J?=9.3Hz,?1H),?3.43?(s,?3H),?2.96?(d,?
J?=2.1Hz,?1H),?2.44?(d,?
J?=9.3Hz,?1H).?IR(KBr):3457,?2935,?2873,?1819,?1724,?1633,?1454,?1381,?1273,?1197,?1168,?1126,?1091,?1033,?988,?917,?871,?808,?754,?699,?654,?577,?523?cm
-。
The preparation of (3) 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides
In the there-necked flask of 2000ml, take by weighing 20g 4,6-O-benzal-alpha-D-glucose first glycosides, add 1600ml N, dinethylformamide is made solvent, take by weighing 4 again, the NaH of 6-O-benzal-1.5 times of amounts of alpha-D-glucose first glycosides molar weight joins in the aforementioned mixing solutions several times, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-1.5 times of amounts of alpha-D-glucose first glycosides molar weight reacted 12 hours down at 45 ~ 60 ℃, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying then, filter, the pressure reducing and steaming solvent, (sherwood oil: ethyl acetate=3:1) separation obtains lurid solid (21.7g) to column chromatography, is 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides.Yield is 74.6%.
Above-mentioned synthetic 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(CDCl
3,?400?MHz)，δ?(ppm):7.52-7.48?(m,?2H),?7.38-7.33?(m,?2H),?7.27?(s,?1H),?5.65?(s,?1H),?4.86-4.84?(m,?1H),?4.69-4.63?(m,?1H),?4.29?(dd,?
J?=4.8?4.4Hz,?1H),?4.16-3.63?(m,?9H),?3.59-3.49?(m,?2H),?3.46-3.45?(d,?
J?=3.2Hz,?3H),?1.86-1.68?(m,?3H),?1.65-1.49?(m,?4H).?IR(KBr):3419,?2938,?2912,?2867,?1647,?1562,?1452,?1376,?1213,?1122,?1088,?1062,?990,?923,?873,?798,?752,?696,?651,?584,?519?cm
-
(4) preparation of 2-O-hydroxyethyl-D-glucose
In the single port flask of 1000ml, add 30g 4 successively, the dilute hydrochloric acid 750ml(1g:25ml of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 1mol/L), reflux 12 hours.After being cooled to room temperature, the pH value that adds 1mol/L sodium hydroxide solution adjusting mixing solutions again is about 6, underpressure distillation boils off and desolventizes, with the methanol solution extraction, use anhydrous magnesium sulfate drying then again, filter, the pressure reducing and steaming solvent, (ethyl acetate: methyl alcohol=3:1) separate, recrystallization obtains white solid (12.6g) to column chromatography, is target product.Yield is 76.8%.
Above-mentioned synthetic 2-O-hydroxyethyl-D-glucose, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(D
2O,?400?MHz)，δ?(ppm):?5.24-5.23?(d,?
J?=4.00Hz,2H),?4.60?(s,?1H),?3.83-3.78?(m,?1H),?3.71-3.50(m,?12H),3.38?(t,
?J?=8.0Hz,?1H),?3.27-3.16?(m,?4H),2.95-2.90?(m,?1H).?IR(KBr):?3396,?2933,?2881,?1729,?1645,?1464,?1128,?1070,?1036,891,?867,?726,?663cm
-1。
Embodiment 2
(1) preparation of α-Pu Taotang first glycosides
With embodiment 1
The preparation of (2) 4,6-O-benzal-alpha-D-glucose first glycosides
With embodiment 1
The preparation of (3) 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides
In the there-necked flask of 2000ml, take by weighing 20g 4,6-O-benzal-alpha-D-glucose first glycosides, add 1600ml 1, the 4-dioxane is made solvent, take by weighing 4 again, the NaH of 6-O-benzal-2 times of amounts of alpha-D-glucose molar weight joins in the aforementioned mixing solutions several times, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-1.5 times of amounts of alpha-D-glucose quality reacted 12 hours down at 45 ~ 60 ℃, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying then, filter, the pressure reducing and steaming solvent, (sherwood oil: ethyl acetate=3:1) separation obtains lurid solid (7.2g) to column chromatography, is 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides.Yield is 24.8%.
Above-mentioned synthetic 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(CDCl
3,?400?MHz)，δ?(ppm):7.52-7.48?(m,?2H),?7.38-7.33?(m,?2H),?7.27?(s,?1H),?5.65?(s,?1H),?4.86-4.84?(m,?1H),?4.69-4.63?(m,?1H),?4.29?(dd,?
J?=4.8?4.4Hz,?1H),?4.16-3.63?(m,?9H),?3.59-3.49?(m,?2H),?3.46-3.45?(d,?
J?=3.2Hz,?3H),?1.86-1.68?(m,?3H),?1.65-1.49?(m,?4H).?IR(KBr):3419,?2938,?2912,?2867,?1647,?1562,?1452,?1376,?1213,?1122,?1088,?1062,?990,?923,?873,?798,?752,?696,?651,?584,?519?cm
-
(4) preparation of 2-O-hydroxyethyl-D-glucose
In the single port flask of 2000ml, add 30g 4 successively, the dilute hydrochloric acid 1200ml (1g:40ml) of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 1mol/L, reflux 12 hours.After being cooled to room temperature, the pH value that adds 1mol/L sodium hydroxide solution adjusting mixing solutions again is about 6, underpressure distillation boils off and desolventizes, with the methanol solution extraction, use anhydrous magnesium sulfate drying then again, filter, the pressure reducing and steaming solvent, (ethyl acetate: methyl alcohol=3:1) separate, recrystallization obtains white solid (10.3g) to column chromatography, is target product.Yield is 62.8%.
Above-mentioned synthetic 2-O-hydroxyethyl-D-glucose, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(D
2O,?400?MHz)，δ?(ppm):?5.24-5.23?(d,?
J?=4.00Hz,2H),?4.60?(s,?1H),?3.83-3.78?(m,?1H),?3.71-3.50(m,?12H),3.38?(t,
?J?=8.0Hz,?1H),?3.27-3.16?(m,?4H),2.95-2.90?(m,?1H).?IR(KBr):?3396,?2933,?2881,?1729,?1645,?1464,?1128,?1070,?1036,891,?867,?726,?663cm
-1。
Embodiment 3
(1) preparation of α-Pu Taotang first glycosides
With embodiment 1
(
2) 4, the preparation of 6-O-benzal-alpha-D-glucose first glycosides
With embodiment 1
The preparation of (3) 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides
In the there-necked flask of 2000ml, take by weighing 20g 4,6-O-benzal-alpha-D-glucose first glycosides, add the 1600ml tetrahydrofuran (THF) and make solvent, take by weighing 4 again, the NaH of 6-O-benzal-1.8 times of amounts of alpha-D-glucose molar weight joins in the aforementioned mixing solutions several times, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-2 times of amounts of alpha-D-glucose molar weight, 45 ~ 60 ℃ of down reactions 12 hours, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying then, filter, the pressure reducing and steaming solvent, (sherwood oil: ethyl acetate=3:1) separation obtains lurid solid (4.7g) to column chromatography, be 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides.Yield is 16.2%.
Above-mentioned synthetic 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(CDCl
3,?400?MHz)，δ?(ppm):7.52-7.48?(m,?2H),?7.38-7.33?(m,?2H),?7.27?(s,?1H),?5.65?(s,?1H),?4.86-4.84?(m,?1H),?4.69-4.63?(m,?1H),?4.29?(dd,?
J?=4.8?4.4Hz,?1H),?4.16-3.63?(m,?9H),?3.59-3.49?(m,?2H),?3.46-3.45?(d,?
J?=3.2Hz,?3H),?1.86-1.68?(m,?3H),?1.65-1.49?(m,?4H).?IR(KBr):3419,?2938,?2912,?2867,?1647,?1562,?1452,?1376,?1213,?1122,?1088,?1062,?990,?923,?873,?798,?752,?696,?651,?584,?519?cm
-
(4) preparation of 2-O-hydroxyethyl-D-glucose
In the single port flask of 1000ml, add 30g 4 successively, the dilute hydrochloric acid 900ml (1g:30ml) of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 1mol/L, reflux 12 hours.After being cooled to room temperature, the pH value that adds 1mol/L sodium hydroxide solution adjusting mixing solutions again is about 6, underpressure distillation boils off and desolventizes, with the methanol solution extraction, use anhydrous magnesium sulfate drying then again, filter, the pressure reducing and steaming solvent, (ethyl acetate: methyl alcohol=3:1) separate, recrystallization obtains white solid (11.9g) to column chromatography, is target product.Yield is 72.5%.
Above-mentioned synthetic 2-O-hydroxyethyl-D-glucose, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1HNMR?(D
2O,?400?MHz)，δ?(ppm):?5.24-5.23?(d,?
J?=4.00Hz,2H),?4.60?(s,?1H),?3.83-3.78?(m,?1H),?3.71-3.50(m,?12H),3.38?(t,
?J?=8.0Hz,?1H),?3.27-3.16?(m,?4H),2.95-2.90?(m,?1H).?IR(KBr):?3396,?2933,?2881,?1729,?1645,?1464,?1128,?1070,?1036,891,?867,?726,?663cm
-1。
Embodiment 4
(1) preparation of α-Pu Taotang first glycosides
With embodiment 1
The preparation of (2) 4,6-O-benzal-alpha-D-glucose first glycosides
With embodiment 1
The preparation of (3) 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides
In the there-necked flask of 1000ml, take by weighing 20g 4,6-O-benzal-alpha-D-glucose first glycosides, add the 700ml pyridine and make solvent, take by weighing 4 again, the NaH of 6-O-benzal-2 times of amounts of alpha-D-glucose molar weight joins in the aforementioned mixing solutions several times, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-1.8 times of amounts of alpha-D-glucose molar weight, 45 ~ 60 ℃ of down reactions 12 hours, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying then, filter, the pressure reducing and steaming solvent, (sherwood oil: ethyl acetate=3:1) separation obtains lurid solid (4.3g) to column chromatography, be 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides.Yield is 14.8%.
Above-mentioned synthetic 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides, warp
1HNMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1H?NMR?(CDCl
3,?400?MHz)，δ?(ppm):7.52-7.48?(m,?2H),?7.38-7.33?(m,?2H),?7.27?(s,?1H),?5.65?(s,?1H),?4.86-4.84?(m,?1H),?4.69-4.63?(m,?1H),?4.29?(dd,?
J?=4.8?4.4Hz,?1H),?4.16-3.63?(m,?9H),?3.59-3.49?(m,?2H),?3.46-3.45?(d,?
J?=3.2Hz,?3H),?1.86-1.68?(m,?3H),?1.65-1.49?(m,?4H).?IR(KBr):3419,?2938,?2912,?2867,?1647,?1562,?1452,?1376,?1213,?1122,?1088,?1062,?990,?923,?873,?798,?752,?696,?651,?584,?519?cm
-
(4) preparation of 2-O-hydroxyethyl-D-glucose
In the single port flask of 2000ml, add 30g 4 successively, the dilute hydrochloric acid 1050ml (1g:35ml) of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 1mol/L, reflux 12 hours.After being cooled to room temperature, the pH value that adds 1mol/L sodium hydroxide solution adjusting mixing solutions again is about 6, underpressure distillation boils off and desolventizes, with the methanol solution extraction, use anhydrous magnesium sulfate drying then again, filter, the pressure reducing and steaming solvent, (ethyl acetate: methyl alcohol=3:1) separate, recrystallization obtains white solid (10.6g) to column chromatography, is target product.Yield is 64.6%.
Above-mentioned synthetic 2-O-hydroxyethyl-D-glucose, warp
1H NMR, IR detects, and its product is pure target compound.Its each performance index or characterization data are as follows:
1HNMR?(D
2O,?400?MHz)，δ?(ppm):?5.24-5.23?(d,?
J?=4.00Hz,2H),?4.60?(s,?1H),?3.83-3.78?(m,?1H),?3.71-3.50(m,?12H),3.38?(t,
?J?=8.0Hz,?1H),?3.27-3.16?(m,?4H),2.95-2.90?(m,?1H).?IR(KBr):?3396,?2933,?2881,?1729,?1645,?1464,?1128,?1070,?1036,891,?867,?726,?663cm
-1。
Claims (4)
1. the preparation method of 2-O-hydroxyethyl-D-glucose comprises following processing step:
(1) preparation of α-Pu Taotang first glycosides: alpha-D-glucose is joined in the methanol solution of hydrogenchloride, be heated to 65 ~ 70 ℃ of back flow reaction 48 ~ 72 hours, cooling, underpressure distillation, crystallisation by cooling, suction filtration, Air drying obtains the white powder solid;
(2) 4, the preparation of 6-O-benzal-alpha-D-glucose first glycosides: with the tosic acid is catalyzer, in non-proton organic solvent, with α-Pu Taotang first glycosides and 2, the 2-dimethoxy-p is with the mixed in molar ratio of 1:1 ~ 1:1.5, in 65 ± 5 ℃ of reactions 1 ~ 2 hour of reducing pressure down, the pressure reducing and steaming solvent is used the sodium bicarbonate aqueous solution crystallization, suction filtration, Air drying obtains 4,6-O-benzal-alpha-D-glucose first glycosides;
(3) 4, the preparation of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides: in non-proton organic solvent, earlier with 4,6-O-benzal-alpha-D-glucose first glycosides, sodium hydride is with the mixed in molar ratio of 1:1.2 ~ 1:1.8, when being stirred to no gas and emitting, add 4 again, the tetrahydropyranyl ethers of the ethylene bromohyrin of 6-O-benzal-1.2 ~ 1.5 times of amounts of alpha-D-glucose first glycosides molar weight, 45 ~ 60 ℃ of down reactions 6 ~ 12 hours, add methanol solution and carry out cancellation, use ethyl acetate extraction after boiling off most of solvent, use anhydrous magnesium sulfate drying, filter, the pressure reducing and steaming solvent, column chromatography for separation obtains product;
(4) preparation of 2-O-hydroxyethyl-D-glucose: with 4,6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides with the dilute hydrochloric acid of 0.5 ~ 1mol/L 95 ~ 100 ℃ of following hydrolysis 8 ~ 12 hours, the pH value of sodium hydroxide solution adjusting mixing solutions is 6.5 ~ 7 again, underpressure distillation boils off solvent, use methanol extraction, anhydrous magnesium sulfate drying filters, the pressure reducing and steaming solvent, column chromatography for separation obtains product.
2. the preparation method of 2-O-hydroxyethyl-D-glucose according to claim 1, it is characterized in that: in the methanol solution of hydrogenchloride, the mass percent of hydrogenchloride is 7% ~ 15% described in the step (1); The mole number of methyl alcohol is 16 ~ 17 times of alpha-D-glucose.
3. the preparation method of 2-O-hydroxyethyl-D-glucose according to claim 1, it is characterized in that: non-proton organic solvent is N described in step (2), (3), dinethylformamide, 1,4-dioxane, tetrahydrofuran (THF), pyridine.
4. the preparation method of 2-O-hydroxyethyl-D-glucose according to claim 1, it is characterized in that: step (4) is described 4, and the quality-volume ratio of the dilute hydrochloric acid of 6-O-benzal-2-O-(2-tetrahydro-pyran oxy ethyl)-α-D-Glucopyranose first glycosides and 0.5 ~ 1mol/L is 1g:25ml ~ 1g:40ml.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103588825A (en) * | 2013-11-14 | 2014-02-19 | 大连九信生物化工科技有限公司 | Method for protecting D-glucosamine derivative by using benzaldehyde dimethyl acetal |
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| Title |
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| 章亚东，等: "《乙二醇葡萄糖苷的合成研究》", 《日用化学工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588825A (en) * | 2013-11-14 | 2014-02-19 | 大连九信生物化工科技有限公司 | Method for protecting D-glucosamine derivative by using benzaldehyde dimethyl acetal |
| CN103588825B (en) * | 2013-11-14 | 2016-06-22 | 大连九信生物化工科技有限公司 | A kind of method of benzaldehyde dimethyl acetal protection D-glucosamine derivant |
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