CN103665064B - One prepares the method for 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose - Google Patents
One prepares the method for 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose Download PDFInfo
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Abstract
The present invention relates to sugar compounds field, be specifically related to the method that one prepares 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose.Semi-lactosi, at aceticanhydride and catalyzer, prepares benzothiazolyl thioacetyl semi-lactosi under 2-mercaptobenzothiazole effect.Benzothiazolyl thioacetyl semi-lactosi prepares benzothiazolyl sulfo-tetrabenzyl semi-lactosi under potassium hydroxide and Benzyl Chloride effect.Benzothiazolyl sulfo-tetrabenzyl semi-lactosi prepares 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose under the effect of N-bromo-succinimide.The inventive method, by three-step reaction method synthesis 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, improves purity and the yield of product effectively; Simple to operate, raw material is easy to get, and has saved running cost and material.
Description
Technical field
The present invention relates to sugar compounds field, be specifically related to the method that one prepares 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose.
Background technology
2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, also known as 2,3,4,6-tetra--O-benzyl-D-galactopyranose glycosides, English name: 2,3,4,6-Tetra-O-benzyl-D-galactose, No. CAS: 53081-25-7, molecular formula: C34H36O6, structural formula is as follows:
In the prior art, general semi-lactosi and the Methanol of adopting, for semi-lactosi first glycosides, is then prepared tetrabenzyl semi-lactosi by semi-lactosi first glycosides, is then used triphenyl Tetrafluoroboric acid carbon demethylating.As MildandEfficientChemoselectiveDeprotectionofAnomericO-Me thylGlycosideswithTritylTetrafluoroborate, JournalofOrganicChemistry, 2008, vol.73, #15p.5993 – 5995, aforesaid method catalyzer triphenyl Tetrafluoroboric acid carbon ratio costly, cost is too high, or adopt semi-lactosi to carry out acetylize, then p-methylphenyl thioacetyl semi-lactosi is prepared, through Benzylation, N-bromo-succinimide sloughs toluene-ω-thiol, thus preparation 2, 3, 4, 6-tetra--oxygen-benzyl-D-pyrans (type) semi-lactosi, as SyntheticIminosugarDerivativesasNewPotentialImmunosuppre ssiveAgents, JournalofMedicinalChemistry, 2005, vol.48, #11p.3688 – 3691, toxicity ratio is used stronger in this method, 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 existed 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 and a kind ofly adopt three-step reaction, preparation 2,3 that simple to operate, raw material is easy to get, the method of 4,6-, tetra--oxygen-benzyl-D-galactopyranose.
The present invention is achieved by the following measures:
One prepares the method for 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, comprises the following steps:
A) room temperature adds aceticanhydride and catalyzer, adds semi-lactosi, after having reacted, add 2-mercaptobenzothiazole, be heated to 50-60 DEG C at 10-15 DEG C point 10 batches; Benzothiazolyl thioacetyl semi-lactosi is obtained through aftertreatment.
B) potassium hydroxide and benzothiazolyl thioacetyl semi-lactosi are added in Benzyl Chloride are heated to back flow reaction and complete, reacted rear cooling, obtained benzothiazolyl sulfo-tetrabenzyl semi-lactosi through aftertreatment.
C) benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in acetone dissolves, add water, stir in room temperature and add N-bromo-succinimide, stir 0.5 hour, reacted and obtained 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose through aftertreatment.
Described method, described aceticanhydride: catalyzer: semi-lactosi: the mol ratio of 2-mercaptobenzothiazole is 5.5-6.5:2-3:1:1.1-1.2
Described method, benzothiazolyl thioacetyl semi-lactosi: Benzyl Chloride: the mol ratio of potassium hydroxide is 1:10-15:4-8.
Described method, the mol ratio of benzothiazolyl sulfo-tetrabenzyl semi-lactosi and N-bromo-succinimide is 1:1.1-1.3.
Described method, catalyzer comprises zinc chloride, iron(ic) chloride, zirconium chloride or aluminum chloride.
Described method, in step a, the reaction times is 24-30 hour, and in step b, the reaction times is 4-7 hour.
Described method, in step a, aftertreatment is cancellation, extraction, and washing is concentrated, adds organic solvent crystallization.
Described method, in step b, aftertreatment is for go out with shrend, is extracted with ethyl acetate, and through 3 washings, is concentrated into dry, adds mixed solvent crystallization.
Described method, in step c, aftertreatment adds the sodium carbonate solution of 5% after being, separates organic layer, and aqueous layer with ethyl acetate extracts, and separates organic phase, through concentrated, adds mixed solvent crystallization.
Described method, in step a, described organic solvent is t-butyl methyl ether, methyl alcohol or ethanol.
In described method steps b, mixed solvent is mol ratio is the t-butyl methyl ether of 2:4-6 and the solvent mixture of isohexane.
Described method, in step c, mixed solvent is mol ratio is the t-butyl methyl ether of 2:2-3 and the solvent mixture of isohexane.
Beneficial effect: the inventive method adopts different reaction systems, comprises reaction raw materials, treatment process etc., is obtained by reacting product by means of only 3 steps, effectively improves purity and the yield of product; Simple to operate, raw material is easy to get, and has saved running cost and material.
Accompanying drawing explanation
Accompanying drawing 1 is the nuclear magnetic spectrogram of product 2,3,4, the 6-tetra--O-benzyl-D-galactopyranose glycosides that embodiment 1 prepares.
Embodiment
In order to further understand the present invention, be described below in conjunction with the process of specific embodiment to this programme, but should be appreciated that these describe just in order to further instruction the features and advantages of the present invention, instead of limiting to the claimed invention.
Embodiment 15.5:2:1:1.1
A) room temperature adds 5.5mol aceticanhydride and 2mol zinc chloride, adds 1mol semi-lactosi at 10-15 DEG C point 10 batches, after having reacted, adds 1.1mol2-mercaptobenzothiazole, is heated to 50-60 DEG C; 0.87mol benzothiazolyl thioacetyl semi-lactosi is obtained through aftertreatment.
B) 3.48mol potassium hydroxide and 0.87mol benzothiazolyl thioacetyl semi-lactosi are added in 8.7mol Benzyl Chloride be heated to backflow, reacted rear cooling, obtained 0.79mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi through aftertreatment.
C) 0.79mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in 4mol acetone dissolves, add 2mol water, stir in room temperature and add 0.87molN-bromo-succinimide, stir 0.5 hour, react and obtained 0.71mol2 through aftertreatment, 3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 71%.
In step a, aftertreatment is that the water of 0-5 DEG C dripping 10mol stirs 2 hours, by the extraction into ethyl acetate aqueous layer extracted of 5mol, separates organic phase 10mol water washing organic phase, separates organic phase and concentrate, add the crystallization of 1mol t-butyl methyl ether, filter, dry.
In step b, aftertreatment for add 5mol water in reaction system, stir 30 minutes, by the extraction into ethyl acetate aqueous layer extracted of 5mol, separate organic phase 5mol water washing organic phase, wash three times, separate organic phase and concentrate, be concentrated into dry, add the t-butyl methyl ether of 0.2mol and the crystallization of 0.4mol isohexane, filter, dry.
In step c, aftertreatment adds the sodium carbonate solution of 3mol5% after being, separate organic layer, water layer 3mol extraction into ethyl acetate, separate organic phase, merge organic phase, with the water washing of 5mol, separate organic phase to concentrate, add the t-butyl methyl ether of 0.2mol and the crystallization of 0.3mol isohexane, filter, dry
Embodiment 26:2:1:1.2
A) room temperature adds 6mol aceticanhydride and 2mol zinc chloride, adds 1mol semi-lactosi at 10-15 DEG C point 10 batches, after having reacted, adds 1.2mol2-mercaptobenzothiazole, is heated to 50-60 DEG C; 0.88mol benzothiazolyl thioacetyl semi-lactosi is obtained through aftertreatment.
B) 3.6mol potassium hydroxide and 0.88mol benzothiazolyl thioacetyl semi-lactosi are added in 9.2mol Benzyl Chloride be heated to backflow, reacted rear cooling, obtained 0.81mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi through aftertreatment.
C) 0.81mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in 4mol acetone dissolves, add 2mol water, stir in room temperature and add 0.94molN-bromo-succinimide, stir 0.5 hour, react and obtained 0.72mol2 through aftertreatment, 3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 72%.
In step a, aftertreatment is that the water of 0-5 DEG C dripping 10mol stirs 2 hours, by the extraction into ethyl acetate aqueous layer extracted of 5mol, separates organic phase 10mol water washing organic phase, separates organic phase and concentrate, add the crystallization of 1mol t-butyl methyl ether, filter, dry.
In step b, aftertreatment for add 5mol water in reaction system, stir 30 minutes, by the extraction into ethyl acetate aqueous layer extracted of 5mol, separate organic phase 5mol water washing organic phase, wash three times, separate organic phase and concentrate, be concentrated into dry, add the t-butyl methyl ether of 0.2mol and the crystallization of 0.4mol isohexane, filter, dry.
In step c, aftertreatment adds the sodium carbonate solution of 3mol5% after being, separate organic layer, water layer 3mol extraction into ethyl acetate, separate organic phase, merge organic phase, with the water washing of 5mol, separate organic phase to concentrate, add the t-butyl methyl ether of 0.2mol and the crystallization of 0.3mol isohexane, filter, dry
Embodiment 36.5:2:1:1.2
A) room temperature adds 65mol aceticanhydride and 20mol aluminum chloride, adds 10mol semi-lactosi at 10-15 DEG C point 10 batches, after having reacted, adds 12mol2-mercaptobenzothiazole, is heated to 50-60 DEG C; 8.9mol benzothiazolyl thioacetyl semi-lactosi is obtained through aftertreatment.
B) 44.5mol potassium hydroxide and 8.9mol benzothiazolyl thioacetyl semi-lactosi are added in 106.8mol Benzyl Chloride be heated to backflow, reacted rear cooling, obtained 8.25mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi through aftertreatment.
C) 8.25mol benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in 40mol acetone dissolves, add 20mol water, stir in room temperature and add 9.6molN-bromo-succinimide, stir 0.5 hour, react and obtained 7.33mol2 through aftertreatment, 3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 73.3%.
In step a, aftertreatment is that the water of 0-5 DEG C dripping 100mol stirs 2 hours, by the extraction into ethyl acetate aqueous layer extracted of 50mol, separates organic phase 100mol water washing organic phase, separates organic phase and concentrate, add the crystallization of 10mol t-butyl methyl ether, filter, dry.
In step b, aftertreatment for add 50mol water in reaction system, stir 30 minutes, by the extraction into ethyl acetate aqueous layer extracted of 50mol, separate organic phase 50mol water washing organic phase, wash three times, separate organic phase and concentrate, 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 30mol5% after being, separates organic layer, and water layer 30mol extraction into ethyl acetate, separates organic phase, merge organic phase, with the water washing of 05mol, separate organic phase and concentrate, add the t-butyl methyl ether of 2mol and the crystallization of 3mol isohexane, filter, dry
Embodiment 4 comparative examples
A) room temperature adds 6mol aceticanhydride and 2mol zinc chloride, adds 1mol semi-lactosi at 10-15 DEG C point 10 batches, after having reacted, adds 1.2mol toluene-ω-thiol, is heated to 50-60 DEG C; 0.75mol p-methylphenyl thioacetyl semi-lactosi is obtained through aftertreatment.
B) 3mol potassium hydroxide and 0.75mol p-methylphenyl thioacetyl semi-lactosi are added in 7.5mol Benzyl Chloride be heated to backflow, reacted rear cooling, obtained 0.71mol p-methylphenyl sulfo-tetrabenzyl semi-lactosi through aftertreatment.
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 0.94molN-bromo-succinimide, stir 0.5 hour, react and obtained 0.62mol2 through aftertreatment, 3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 62%.
Claims (5)
1. prepare the method for 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose for one kind, it is characterized in that comprising the following steps:
A) in reaction vessel, add aceticanhydride and catalyzer under room temperature, add semi-lactosi at 10-15 DEG C point 10 batches, after having reacted, add 2-mercaptobenzothiazole, be heated to 50-60 DEG C; Benzothiazolyl thioacetyl semi-lactosi is obtained through aftertreatment;
B) potassium hydroxide and benzothiazolyl thioacetyl semi-lactosi are added in Benzyl Chloride are heated to back flow reaction and complete, reacted rear cooling, obtained benzothiazolyl sulfo-tetrabenzyl semi-lactosi through aftertreatment;
C) benzothiazolyl sulfo-tetrabenzyl semi-lactosi is added in acetone dissolves, add water, stir in room temperature and add N-bromo-succinimide, stir 0.5 hour, reacted and obtained 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose through aftertreatment;
Aceticanhydride in step a): catalyzer: semi-lactosi: the mol ratio of 2-mercaptobenzothiazole is 5.5-6.5:2-3:1:1.1-1.2;
Benzothiazolyl thioacetyl semi-lactosi in step b): Benzyl Chloride: the mol ratio of potassium hydroxide is 1:10-15:4-8;
In step c), the mol ratio of benzothiazolyl sulfo-tetrabenzyl semi-lactosi and N-bromo-succinimide is 1:1.1-1.3;
Catalyzer is more than one in zinc chloride, iron(ic) chloride, zirconium chloride and aluminum chloride;
In step a), the reaction times is 24-30 hour, and in step b), the reaction times is 4-7 hour.
2. method according to claim 1, is characterized in that in step a), aftertreatment is cancellation, extraction, and washing is concentrated, adds organic solvent crystallization.
3. method according to claim 1, is characterized in that in step b), aftertreatment is for go out with shrend, is extracted with ethyl acetate, and through 3 washings, is concentrated into dry, adds mixed solvent crystallization.
4. method according to claim 1, is characterized in that in step c), aftertreatment adds the sodium carbonate solution of 5% after being, separates organic layer, and aqueous layer with ethyl acetate extracts, and separates organic phase, through concentrated, adds mixed solvent crystallization.
5. method according to claim 4, is characterized in that in step c), and mixed solvent is mol ratio is the t-butyl methyl ether of 2:2-3 and the solvent mixture of isohexane.
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| CN112262148A (en) * | 2018-06-11 | 2021-01-22 | 阿尔第实业有限公司 | Improved process for the preparation of 2,3,4, 6-tetra-O-benzyl-D-galactose |
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| 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 |
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| 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 |
| CN1715286A (en) * | 2004-07-02 | 2006-01-04 | 北京大学 | Synthetic method for pentose antigen for inhibiting heterogenic organ transplant immune rejection 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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