CN103694287B - The technique of preparation 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose - Google Patents
The technique of preparation 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose Download PDFInfo
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- CN103694287B CN103694287B CN201310670880.9A CN201310670880A CN103694287B CN 103694287 B CN103694287 B CN 103694287B CN 201310670880 A CN201310670880 A CN 201310670880A CN 103694287 B CN103694287 B CN 103694287B
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Abstract
The present invention relates to sugar compounds field, be specifically related to the method that one is prepared 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose. Galactolipin, at aceticanhydride and catalyst, is prepared benzothiazolyl thioacetyl galactolipin under 2-mercaptobenzothiazole effect. Benzothiazolyl thioacetyl galactolipin prepares benzothiazolyl sulfo-tetrabenzyl galactolipin under potassium hydroxide and benzyl chloride effect. Benzothiazolyl sulfo-tetrabenzyl galactolipin is prepared 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose under the effect of N-bromo-succinimide. The inventive method, by synthetic 2,3,4,6-, the tetra--oxygen-benzyl-D-galactopyranose of three-step reaction method, has improved 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 one and prepare 2,3,4,6-, tetra--oxygen-benzyl-D-pyrans galaThe technique of sugar.
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, No. CAS: 53081-25-7, molecular formula:C34H36O6，
In the prior art, generally adopt galactolipin and Methanol for galactolipin first glycosides, then prepared by galactolipin first glycosidesTetrabenzyl galactolipin, then uses triphenyl tetrafluoro boric acid carbon demethylating. As MildandEfficientChemoselectiveDeprotectionofAnomericO-MethylGlycosideswithTritylTetrafluoroborate，JournalofOrganicChemistry,2008,vol.73,#15p.5993 – 5995, said method catalyst triphenyl tetrafluoro boric acid carbon ratio is more expensive, and cost is too high, or adopts galactolipin to enterRow acetylation, then prepares p-methylphenyl thioacetyl galactolipin, and through benzyl, N-bromo-succinimide is sloughed tolueneThiophenol, thereby preparation 2,3,4,6-, tetra--oxygen-benzyl-D-pyrans (type) galactolipin, as SyntheticIminosugarDerivativesasNewPotentialImmunosuppressiveAgents，JournalofMedicinalChemistry, 2005, vol.48, #11p.3688 – 3691, uses toxicity in this method more intense, smellLarger toluene-ω-thiol.
Summary of the invention
In order to solve in above prior art 2,3,4, in the preparation of 6-tetra--oxygen-benzyl-D-pyrans (type) galactolipin, existCost compare high, the present situation that yield is lower, the invention provides a kind of three-step reaction, simple to operate, raw material of adopting and is easy to getPreparation 2,3,4, the technique of 6-tetra--oxygen-benzyl-D-galactopyranose.
The present invention is achieved by the following measures:
The technique of preparation 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, comprises the following steps:
A) room temperature adds aceticanhydride and catalyst, adds galactolipin at 10-15 DEG C point 8 batches, after having reacted, adds 2-sulfydrylBenzothiazole, is heated to 50-60 DEG C; Obtain benzothiazolyl thioacetyl galactolipin through post processing.
B) potassium hydroxide and benzothiazolyl thioacetyl galactolipin are added to and in benzyl chloride, are heated to back flow reaction and complete,React rear cooling, obtained benzothiazolyl sulfo-tetrabenzyl galactolipin through post processing.
C) benzothiazolyl sulfo-tetrabenzyl galactolipin is added in acetone and is dissolved, add water, stir in room temperature and add N-Bromo-succinimide, stirs 0.5 hour, has reacted through post processing and has obtained 2,3,4,6-, tetra--oxygen-benzyl-D-pyrans halfLactose.
Described technique, described aceticanhydride: catalyst: galactolipin: the mol ratio of 2-mercaptobenzothiazole is 6.5:2:1:1.2
Described technique, benzothiazolyl thioacetyl galactolipin: benzyl chloride: the mol ratio of potassium hydroxide is 1:10-15:4-8。
Described technique, the mol ratio of benzothiazolyl sulfo-tetrabenzyl galactolipin and N-bromo-succinimide is 1:1.1-1.3。
Described technique, catalyst comprises zinc chloride, iron chloride, zirconium chloride or aluminium chloride.
Described technique, in step a, the reaction time is 24-30 hour, in step b, the reaction time is 4-7 hour.
Described technique, in step a, post processing is cancellation, extraction, washing, concentrated, add organic solvent crystallization.
Described technique, in step b, post processing is water cancellation, is extracted with ethyl acetate, and through 3 washings, is concentrated intoDry, add mixed solvent crystallization.
Described technique, in step c, post processing adds 5% sodium carbonate liquor after being, separates organic layer, water layer acetic acidEthyl ester extraction, 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 mixing of isohexaneAnd solvent.
Described technique, in step c, mixed solvent is that mol ratio is the t-butyl methyl ether of 2:2-3 and mixing of isohexaneAnd solvent.
Beneficial effect: the reaction system that process using of the present invention is different, comprise reaction raw materials, processing methods etc., only by 3Step reaction obtains product, has effectively improved purity and the yield of product; Simple to operate, raw material is easy to get, and has saved running costAnd material.
Detailed description of the invention
In order further to understand the present invention, below in conjunction with specific embodiment, the process of this programme is described, stillShould be appreciated that these are described is for further instruction the features and advantages of the present invention, instead of right of the present invention is wantedThe restriction of asking.
Embodiment 16.5:2:1:1.2
A) room temperature adds 65mol aceticanhydride and 20mol aluminium chloride, adds 10mol galactolipin at 10-15 DEG C point 8 batches, has reactedCheng Hou, adds 12mol2-mercaptobenzothiazoler, is heated to 50-60 DEG C; Obtain 8.9mol benzothiazolyl sulphur through post processingFor acetyl galactolipin.
B) 44.5mol potassium hydroxide and 8.9mol benzothiazolyl thioacetyl galactolipin are added to 106.8mol benzyl chlorideIn be heated to reflux, react rear cooling, pass through post processing obtain 8.25mol benzothiazolyl sulfo-tetrabenzyl galactolipin.
C) 8.25mol benzothiazolyl sulfo-tetrabenzyl galactolipin is added in 40mol acetone and is dissolved, add 20mol water,Stir in room temperature and add 9.6molN-bromo-succinimide, stir 0.5 hour, reacted through post processing and obtained7.33mol2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, yield is 73.3%.
In step a, post processing is that the water of 0-5 DEG C that drips 100mol stirs 2 hours, by the ethyl acetate extraction extraction of 50molWater intaking layer, separates organic phase 100mol water washing organic phase, separates organic phase concentrated, adds 10mol t-butyl methyl ether knotCrystalline substance, filters, dry.
In step b, post processing, for to add 50mol water in reaction system, is stirred 30 minutes, with the ethyl acetate of 50molExtraction aqueous layer extracted, separates organic phase 50mol water washing organic phase, wash three times, separates organic phase and concentrates, be concentrated into dry,Add the t-butyl methyl ether of 2mol and the crystallization of 4mol isohexane, filter, dry.
In step c, post processing adds the sodium carbonate liquor of 30mol5% after being, separates organic layer, water layer 30mol acetic acidEthyl ester extraction, separates organic phase, merges organic phase, with the water washing of 05mol, separates organic phase concentrated, adds the tertiary fourth of 2molThe crystallization of ylmethyl ether and 3mol isohexane, filters, dry
Control Example
A) room temperature adds 6mol aceticanhydride and 2mol zinc chloride, adds 1mol galactolipin at 10-15 DEG C point 8 batches, and reaction completesAfter, add 1.2mol toluene-ω-thiol, be heated to 50-60 DEG C; Obtain 0.75mol p-methylphenyl thioacetyl through post processingGalactolipin.
B) 3mol potassium hydroxide and 0.75mol p-methylphenyl thioacetyl galactolipin are added in 7.5mol benzyl chloride and are heatedTo refluxing, react rear cooling, obtain 0.71mol p-methylphenyl sulfo-tetrabenzyl galactolipin through post processing.
C) 0.71mol p-methylphenyl sulfo-tetrabenzyl galactolipin is added in 4mol acetone and dissolves, and adds 2mol water, teeter chamberIn temperature, add 0.94molN-bromo-succinimide, stir 0.5 hour, reacted through post processing and obtained 0.62mol2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose, yield is 62%.
Claims (5)
1. prepare the technique of 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose for one kind, it is characterized in that comprising the following steps:
A) under room temperature, in reaction vessel, add aceticanhydride and catalyst, add galactolipin at 10-15 DEG C point 8 batches, after having reacted,Add 2-mercaptobenzothiazole, be heated to 50-60 DEG C; Obtain benzothiazolyl thioacetyl galactolipin through post processing;
B) potassium hydroxide and benzothiazolyl thioacetyl galactolipin are added to and in benzyl chloride, are heated to back flow reaction and complete, reactionCooling after completing, obtains benzothiazolyl sulfo-tetrabenzyl galactolipin through post processing;
C) benzothiazolyl sulfo-tetrabenzyl galactolipin is added in acetone and is dissolved, add water, stir in room temperature and add N-bromoSuccimide, stirs 0.5 hour, has reacted through post processing and has obtained 2,3,4,6-, tetra--oxygen-benzyl-D-galactopyranose;
Aceticanhydride in described step a: catalyst: galactolipin: the mol ratio of 2-mercaptobenzothiazole is 6.5:2:1:1.2;
Benzothiazolyl thioacetyl galactolipin 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 galactolipin and N-bromo-succinimide is 1:1.1-1.3;
Catalyst is more than one in zinc chloride, iron chloride, zirconium chloride and aluminium chloride;
In step a, the reaction time is 24-30 hour, and in step b, the reaction time is 4-7 hour.
2. technique according to claim 1, is characterized in that in step a, post processing is cancellation, extraction, and washing, concentrated, addEnter organic solvent crystallization.
3. technique according to claim 1, is characterized in that in step b, post processing is water cancellation, extracts with ethyl acetateGet, through 3 washings, be concentrated into dryly, add mixed solvent crystallization.
4. technique according to claim 1, is characterized in that post processing in step c adds 5% sodium carbonate liquor after being,Separate organic layer, water layer is extracted with ethyl acetate, and separates organic phase, through concentrated, adds mixed solvent crystallization.
5. technique according to claim 4, is characterized in that in step c, and mixed solvent is that mol ratio is the tertiary fourth of 2:2-3The solvent mixture of ylmethyl ether and isohexane.
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Citations (3)
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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 |
| 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 |
| 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 |
| US20130158242A1 (en) * | 2011-12-16 | 2013-06-20 | National Chiao Tung University | Alpha-selective glycosylation method |
Non-Patent Citations (3)
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| Impact of glycosylation on physicoechemical and biological properties of nitrification inhibitors;Daniele Pro，et al.;《Tetrahedron》;20120621;第68卷;第7095-7102页 * |
| 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;李翔，等;《第二军医大学学报》;20111130;第32卷(第11期);第1227-1230页，尤其是图1，第1228页左栏倒数第2段至第1229页左栏第1段 * |
| Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents;Xin-Shan Ye，et al.;《J. Med. Chem.》;20050504;第48卷(第11期);第3688-3691页，尤其是第3688页方案1 * |
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