CN103709212A - Preparation technology of 2,3,4,6-tetra-oxo-benzyl-D-galactopyranose - Google Patents
Preparation technology of 2,3,4,6-tetra-oxo-benzyl-D-galactopyranose Download PDFInfo
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- CN103709212A CN103709212A CN201310671228.9A CN201310671228A CN103709212A CN 103709212 A CN103709212 A CN 103709212A CN 201310671228 A CN201310671228 A CN 201310671228A CN 103709212 A CN103709212 A CN 103709212A
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Abstract
The invention relates to the field of sugar compounds, and concretely relates to a preparation technology of 2,3,4,6-tetra-oxo-benzyl-D-galactopyranose. The technology comprises the following steps: carrying out a reaction of galactose under the action of acetic anhydride, a catalyst and 2-mercaptobenzothiazole to prepare benzothiazolylthioacetylgalactose; carrying out a reaction of benzothiazolylthioacetylgalactose under the action of potassium hydroxide and benzyl chloride to prepare benzothiazolylthiotetrabenzylgalactose; and carrying out a reaction of benzothiazolylthiotetrabenzylgalactose under the action of N-bromosuccinimide to prepare 2,3,4,6-tetra-oxo-benzyl-D-galactopyranose. The method allows 2,3,4,6-tetra-oxo-benzyl-D-galactopyranose to be synthesized through a three-step reaction, and has the advantages of effective improvement of the purity and the yield of the above product, simple operation, easily available raw materials, and saving of the operation cost and materials.
Description
technical field
The present invention relates to sugar compounds field, be specifically related to a kind of technique of preparing 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose.
background technology
2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, claims again 2,3,4,6-, tetra--O-benzyl-D-galactopyranoside, English name: 2,3,4,6-Tetra-O-benzyl-D-galactose, and No. CAS: 53081-25-7, molecular formula: C34H36O6,
In the prior art, generally adopt semi-lactosi and Methanol for semi-lactosi first glycosides, then by semi-lactosi first glycosides, prepare tetrabenzyl semi-lactosi, then use triphenyl Tetrafluoroboric acid carbon demethylating.As Mild and Efficient Chemoselective Deprotection of Anomeric O-Methyl Glycosides with Trityl Tetrafluoroborate, Journal of Organic Chemistry, 2008, vol. 73, # 15 p. 5993 – 5995, aforesaid method catalyzer triphenyl Tetrafluoroboric acid carbon ratio is more expensive, cost is too high, or adopt semi-lactosi to carry out acetylize, then prepare p-methylphenyl thioacetyl semi-lactosi, through benzyl, N-bromo-succinimide is sloughed toluene-ω-thiol, thereby preparation 2, 3, 4, 6-tetra--oxygen-benzyl-D-pyrans (type) semi-lactosi, as Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents, Journal of Medicinal Chemistry, 2005, vol. 48, # 11 p. 3688 – 3691, in this method, use toxicity more intense, the toluene-ω-thiol that smell is larger.
summary of the invention
In order to solve in above prior art 2,3,4, the cost compare existing in the preparation of 6-tetra--oxygen-benzyl-D-pyrans (type) semi-lactosi is high, the present situation that yield is lower, the invention provides a kind of adopt three-step reaction, the preparation 2,3 that simple to operate, raw material is easy to get, the technique of 4,6-, tetra--oxygen-benzyl-D-galactopyranose.
The present invention is achieved by the following measures:
A kind of technique of preparing 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, comprises the following steps:
A) room temperature adds aceticanhydride and catalyzer, 10-15 ℃ minute 9 batches add semi-lactosi, after having reacted, add 2-mercaptobenzothiazole, be heated to 50-60 ℃; Through aftertreatment, obtain benzothiazolyl thioacetyl semi-lactosi.
B) potassium hydroxide and benzothiazolyl thioacetyl semi-lactosi are added to and in Benzyl Chloride, are heated to back flow reaction and complete, reacted rear cooling, through aftertreatment, obtain benzothiazolyl sulfo-tetrabenzyl semi-lactosi.
C) benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in acetone and is dissolved, add water, stir in room temperature and add N-bromo-succinimide, stir 0.5 hour, reacted through aftertreatment and obtained 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose.
Described technique, described aceticanhydride: catalyzer: semi-lactosi: the mol ratio of 2-mercaptobenzothiazole is 6.5: 2:1:1.2
Described technique, benzothiazolyl thioacetyl semi-lactosi: Benzyl Chloride: the mol ratio of potassium hydroxide is 1:10-15: 4-8.
Described technique, the mol ratio of benzothiazolyl sulfo-tetrabenzyl semi-lactosi and N-bromo-succinimide is 1:1.1-1.3.
Described technique, catalyzer comprises zinc chloride, iron(ic) chloride, zirconium chloride or aluminum chloride.
Described technique, in step a, the reaction times is 24-30 hour, in step b, the reaction times is 4-7 hour.
Described technique, in step a, aftertreatment is cancellation, extraction, washing, concentrated, add organic solvent crystallization.
Described technique, in step b, aftertreatment is water cancellation, is extracted with ethyl acetate, and through 3 washings, is concentrated into dryly, adds mixed solvent crystallization.
Described technique, in step c, aftertreatment adds 5% sodium carbonate solution after being, separates organic layer, and water layer is extracted with ethyl acetate, and separates organic phase, through concentrated, adds mixed solvent crystallization.
Described technique, in step a, described organic solvent is t-butyl methyl ether, methyl alcohol or ethanol.
In described processing step b, mixed solvent is that mol ratio is the t-butyl methyl ether of 2:4-6 and the solvent mixture of isohexane.
Described technique, in step c, mixed solvent is that mol ratio is the t-butyl methyl ether of 2:2-3 and the solvent mixture of isohexane.
Beneficial effect: the reaction system that process using of the present invention is different, comprise reaction raw materials, treatment processs etc., only obtain product by 3 step reactions, have effectively improved purity and the yield of product; Simple to operate, raw material is easy to get, and has saved running cost and material.
Embodiment
In order further to understand the present invention, below in conjunction with specific embodiment, the process of this programme is described, but should be appreciated that these are described is for further instruction the features and advantages of the present invention, rather than limiting to the claimed invention.
embodiment 1 6.5: 2: 1:1.2
A) room temperature adds 65mol aceticanhydride and 20mol aluminum chloride, 10-15 ℃ minute 9 batches add 10mol semi-lactosi, after having reacted, add 12mol 2-mercaptobenzothiazole, be heated to 50-60 ℃; Through aftertreatment, obtain 8.9mol benzothiazolyl thioacetyl semi-lactosi.
B) 44.5mol potassium hydroxide and 8.9mol benzothiazolyl thioacetyl semi-lactosi are added in 106.8mol Benzyl Chloride and are heated to reflux, react rear cooling, pass through aftertreatment and obtain 8.25mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi.
C) 8.25mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in 40mol acetone and is dissolved, add 20mol water, stir in room temperature and add 9.6mol N-bromo-succinimide, stir 0.5 hour, reacted through aftertreatment and obtained 7.33mol2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 73.3%.
In step a, aftertreatment is stirred 2 hours for dripping the water of 0-5 ℃ of 100mol, and the ethyl acetate extraction aqueous layer extracted with 50mol, separates 100mol water washing organic phase for organic phase, separates organic phase concentrated, adds the crystallization of 10mol t-butyl methyl ether, filters, dry.
In step b, aftertreatment for to add 50mol water in reaction system, stir 30 minutes, ethyl acetate extraction aqueous layer extracted with 50mol, separate 50mol water washing organic phase for organic phase, wash three times, separate organic phase concentrated, be concentrated into dry, add the t-butyl methyl ether of 2mol and the crystallization of 4mol isohexane, filter, dry.
In step c, aftertreatment adds the sodium carbonate solution of 30mol 5% after being, separate organic layer, 30mol ethyl acetate extraction for water layer, separate organic phase, merge organic phase, with the water washing of 05mol, separate organic phase concentrated, add the t-butyl methyl ether of 2mol and the crystallization of 3mol isohexane, filter, dry
control Example
A) room temperature adds 6mol aceticanhydride and 2mol zinc chloride, 10-15 ℃ minute 9 batches add 1mol semi-lactosi, after having reacted, add 1.2mol toluene-ω-thiol, be heated to 50-60 ℃; Through aftertreatment, obtain 0.75mol p-methylphenyl thioacetyl semi-lactosi.
B) 3mol potassium hydroxide and 0.75mol p-methylphenyl thioacetyl semi-lactosi are added in 7.5mol Benzyl Chloride and are heated to reflux, react rear cooling, pass through aftertreatment and obtain 0.71mol p-methylphenyl sulfo-tetrabenzyl semi-lactosi.
C) 0.71mol p-methylphenyl sulfo-tetrabenzyl semi-lactosi is added in 4mol acetone and dissolves, add 2mol water, stir in room temperature and add 0.94mol N-bromo-succinimide, stir 0.5 hour, reacted through aftertreatment and obtained 0.62mol2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 62%.
Claims (8)
1. a technique of preparing 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, is characterized in that comprising the following steps:
A) under room temperature, in reaction vessel, add aceticanhydride and catalyzer, 10-15 ℃ minute 9 batches add semi-lactosi, after having reacted, add 2-mercaptobenzothiazole, be heated to 50-60 ℃; Through aftertreatment, obtain benzothiazolyl thioacetyl semi-lactosi;
B) potassium hydroxide and benzothiazolyl thioacetyl semi-lactosi are added to and in Benzyl Chloride, are heated to back flow reaction and complete, reacted rear cooling, through aftertreatment, obtain benzothiazolyl sulfo-tetrabenzyl semi-lactosi;
C) benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in acetone and is dissolved, add water, stir in room temperature and add N-bromo-succinimide, stir 0.5 hour, reacted through aftertreatment and obtained 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose;
Aceticanhydride in described step a: catalyzer: semi-lactosi: the mol ratio of 2-mercaptobenzothiazole is 6.5:2:1:1.2;
Benzothiazolyl thioacetyl semi-lactosi in step b: Benzyl Chloride: the mol ratio of potassium hydroxide is 1:10-15: 4-8.
2. technique according to claim 1, is characterized in that in step c, the mol ratio of benzothiazolyl sulfo-tetrabenzyl semi-lactosi and N-bromo-succinimide is 1:1.1-1.3.
3. technique according to claim 1, described technique, catalyzer is more than one in zinc chloride, iron(ic) chloride, zirconium chloride and aluminum chloride.
4. technique according to claim 1, is characterized in that, in step a, the reaction times is 24-30 hour, and in step b, the reaction times is 4-7 hour.
5. technique according to claim 1, is characterized in that in step a, aftertreatment is cancellation, extraction, and washing, concentrated, add organic solvent crystallization.
6. technique according to claim 1, is characterized in that in step b, aftertreatment is water cancellation, is extracted with ethyl acetate, and through 3 washings, is concentrated into dryly, adds mixed solvent crystallization.
7. technique according to claim 1, is characterized in that aftertreatment in step c adds 5% sodium carbonate solution after being, separates organic layer, and water layer is extracted with ethyl acetate, and separates organic phase, through concentrated, adds mixed solvent crystallization.
8. technique according to claim 7, is characterized in that in step c, and mixed solvent is that mol ratio is the t-butyl methyl ether of 2:2-3 and the solvent mixture of isohexane.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1590394A (en) * | 2003-09-01 | 2005-03-09 | 北京大学 | New type trisaccharide and penta saccharid oligo saccharide antigen, their synthesis method and application in preparation of medicine for inhibiting exclusion reaction |
| CN101775051A (en) * | 2010-01-07 | 2010-07-14 | 北京大学 | Method for regioselectively removing O-benzyl protective group of sugar |
| US20130158242A1 (en) * | 2011-12-16 | 2013-06-20 | National Chiao Tung University | Alpha-selective glycosylation method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1590394A (en) * | 2003-09-01 | 2005-03-09 | 北京大学 | New type trisaccharide and penta saccharid oligo saccharide antigen, their synthesis method and application in preparation of medicine for inhibiting exclusion reaction |
| CN101775051A (en) * | 2010-01-07 | 2010-07-14 | 北京大学 | Method for regioselectively removing O-benzyl protective group of sugar |
| US20130158242A1 (en) * | 2011-12-16 | 2013-06-20 | National Chiao Tung University | Alpha-selective glycosylation method |
Non-Patent Citations (3)
| Title |
|---|
| DANIELE PRO，等: "Impact of glycosylation on physicoechemical and biological properties of nitrification inhibitors", 《TETRAHEDRON》, vol. 68, 21 June 2012 (2012-06-21), XP028426172, DOI: 10.1016/j.tet.2012.06.060 * |
| XIN-SHAN YE，等: "Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents", 《J. MED. CHEM.》, vol. 48, no. 11, 4 May 2005 (2005-05-04), pages 3688 - 1 * |
| 李翔，等: "N-（9-芴甲氧羰基）-O-（2,3,4,6-四苄基-α-D-半乳糖基）-L-丝氨酸的合成", 《第二军医大学学报》, vol. 32, no. 11, 30 November 2011 (2011-11-30) * |
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