CN103694290B - The preparation method of 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose - Google Patents
The preparation method of 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose Download PDFInfo
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- CN103694290B CN103694290B CN201310671212.8A CN201310671212A CN103694290B CN 103694290 B CN103694290 B CN 103694290B CN 201310671212 A CN201310671212 A CN 201310671212A CN 103694290 B CN103694290 B CN 103694290B
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Abstract
The present invention relates to sugar compounds field, be specifically related to one and prepare 2, the method for 3,4,6 four oxygen benzyl D galactopyranoses.Benzothiazolyl thioacetyl galactose prepared under acetic anhydride and catalyst, 2 mercaptobenzothiazoler effects by galactose.Benzothiazolyl thioacetyl galactose prepares benzothiazolyl sulfur for tetrabenzyl galactose under potassium hydroxide and benzyl chloride effect.Benzothiazolyl sulfur prepares 2,3,4,6 4 oxygen benzyl D galactopyranoses for tetrabenzyl galactose under N bromo-succinimide effect.The inventive method synthesizes 2,3,4,6 four oxygen benzyl D galactopyranoses by three-step reaction method, is effectively improved purity and the yield of product；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 a kind of 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose
Preparation method.
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。
In the prior art, general employing galactose and methanol prepare galactose first glycosides, are then prepared by galactose first glycosides
Tetrabenzyl galactose, then with triphenyl Tetrafluoroboric acid carbon demethylating.Such 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, costly, cost is the highest for said method catalyst triphenyl Tetrafluoroboric acid carbon ratio, or uses galactose to enter
Row acetylation, then prepares p-methylphenyl thioacetyl galactose, and through Benzylation, N-bromo-succinimide is sloughed toluene
Thiophenol, thus prepare 2,3,4,6-tetra--oxygen-benzyl-D-pyrans (type) galactose, such as Synthetic Iminosugar
Derivatives as New Potential Immunosuppressive Agents, Journal of Medicinal
Chemistry, 2005, vol. 48, # 11 p. 3,688 3691, use toxicity in this method stronger, abnormal smells from the patient
Bigger toluene-ω-thiol.
Summary of the invention
In order to solve that the preparation of 2,3,4,6-tetra--oxygen in above prior art-benzyl-D-pyrans (type) galactose exists
Cost higher, yield, than relatively low present situation, the invention provides and a kind of uses three-step reaction, simple to operate, raw material to be easy to get
The preparation method of 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose.
The present invention is achieved by the following measures:
The preparation method of 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, comprises the following steps:
A) room temperature adds acetic anhydride and catalyst, adds galactose at 10-15 DEG C point 8 batches, after having reacted, adds 2-sulfydryl
Benzothiazole, is heated to 50-60 DEG C；Benzothiazolyl thioacetyl galactose is obtained through post processing.
B) potassium hydroxide and benzothiazolyl thioacetyl galactose are added in benzyl chloride be heated to back flow reaction complete,
Lower the temperature after having reacted, obtain benzothiazolyl sulfur for tetrabenzyl galactose through post processing.
C) being added in acetone dissolve for tetrabenzyl galactose by benzothiazolyl sulfur, add water, teeter chamber's warming middle-JIAO adds N-
Bromo-succinimide, stirs 0.5 hour, has reacted and obtained 2 through post processing, 3,4,6-tetra--oxygen-benzyl-D-pyrans half
Lactose.
Described method, described acetic anhydride: catalyst: galactose: the mol ratio of 2-mercaptobenzothiazole is 5.5:2:1:
1.1。
Described method, benzothiazolyl thioacetyl galactose: benzyl chloride: the mol ratio of potassium hydroxide is 1:10-
15 :4-8。
Described method, benzothiazolyl sulfur is 1 for the mol ratio of tetrabenzyl galactose Yu N-bromo-succinimide:
1.1-1.3。
Described method, catalyst includes zinc chloride, iron chloride, zirconium chloride or aluminum chloride.
Described method, in step a, the response time is 24-30 hour, and in step b, the response time is 4-7 hour.
Described method, in step a, post processing is cancellation, extraction, and washing concentrates, adds organic solvent crystallization.
Described method, in step b, post processing is for go out with shrend, is extracted with ethyl acetate, and through 3 washings, is concentrated into
Dry, add mixed solvent crystallize.
Described method, adds the sodium carbonate liquor of 5%, separates organic layer, water layer acetic acid after post processing is in step c
Ethyl ester extracts, and separates organic facies, through concentrating, adds mixed solvent crystallize.
Described method, in step a, described organic solvent is t-butyl methyl ether, methanol or ethanol.
In described method step b, mixed solvent be mol ratio be the mixed of the t-butyl methyl ether of 2:4-6 and isohexane
And solvent.
Described method, in step c, mixed solvent be mol ratio be the mixed of the t-butyl methyl ether of 2:2-3 and isohexane
And solvent.
Beneficial effect: the inventive method uses different reaction systems, including reaction raw materials, processing method etc., only by 3
Step reaction obtains product, is effectively improved purity and the yield of product；Simple to operate, raw material is easy to get, and has saved running cost
And material.
Detailed description of the invention
In order to further understand the present invention, below in conjunction with specific embodiment, the process of this programme is described, but
Should be appreciated that these describe be intended merely to further instruction the features and advantages of the present invention rather than right of the present invention is wanted
The restriction asked.
Embodiment 1 5.5: 2: 1:1.1
A) room temperature adds 5.5mol acetic anhydride and 2mol zinc chloride, adds 1mol galactose at 10-15 DEG C point 8 batches, has reacted
Cheng Hou, adds 1.1mol 2-mercaptobenzothiazole, is heated to 50-60 DEG C；0.87mol benzothiazolyl is obtained through post processing
Thioacetyl galactose.
B) 3.48mol potassium hydroxide and 0.87mol benzothiazolyl thioacetyl galactose are added to 8.7mol benzyl chloride
In be heated to backflow, after react cooling, obtain 0.79mol benzothiazolyl sulfur for tetrabenzyl galactose through post processing.
C) it is added in 4mol acetone dissolve for tetrabenzyl galactose by 0.79mol benzothiazolyl sulfur, adds 2mol water, stir
Mix addition 0.87mol N-bromo-succinimide in room temperature, stir 0.5 hour, reacted and obtained through post processing
0.71mol2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 71%.
In step a, post processing is that the water of dropping 0-5 DEG C of 10mol stirs 2 hours, with the extraction of the ethyl acetate of 5mol
Water layer, separates organic facies 10mol water washing organic facies, separates organic facies and concentrate, add the crystallization of 1mol t-butyl methyl ether, mistake
Filter, is dried.
In step b, post processing is addition 5mol water in reaction system, stirs 30 minutes, extracts by the ethyl acetate of 5mol
Take aqueous layer extracted, separate organic facies 5mol water washing organic facies, wash three times, separate organic facies and concentrate, be concentrated to dryness, add
The t-butyl methyl ether of 0.2mol and the crystallize of 0.4mol isohexane, filter, and is dried.
Add the sodium carbonate liquor of 3mol 5% after post processing is in step c, separate organic layer, water layer 3mol acetic acid second
Ester extracts, and separates organic facies, merges organic facies, washs with the water of 5mol, separates organic facies and concentrates, adds the tert-butyl group of 0.2mol
Methyl ether and the crystallize of 0.3mol isohexane, filter, and is dried.
Comparative examples
A) room temperature adds 6mol acetic anhydride and 2mol zinc chloride, adds 1mol galactose at 10-15 DEG C point 8 batches, and reaction completes
After, add 1.2mol toluene-ω-thiol, be heated to 50-60 DEG C；0.75mol p-methylphenyl thioacetyl is obtained through post processing
Galactose.
B) 3mol potassium hydroxide and 0.75mol p-methylphenyl thioacetyl galactose are added in 7.5mol benzyl chloride heating
To backflow, lower the temperature after having reacted, obtain 0.71mol p-methylphenyl sulfur for tetrabenzyl galactose through post processing.
C) 0.71mol p-methylphenyl sulfur is added in 4mol acetone dissolve for tetrabenzyl galactose, adds 2mol water, teeter chamber
Warming middle-JIAO adds 0.94mol N-bromo-succinimide, stirs 0.5 hour, has reacted and obtained 0.62mol2 through post processing,
3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 62%.
Claims (2)
1. one kind 2, the preparation method of 3,4,6-tetra--oxygen-benzyl-D-galactopyranose, it is characterized in that comprising the following steps:
A) in reaction vessel, add acetic anhydride and catalyst under room temperature, add galactose at 10-15 DEG C point 8 batches, after having reacted,
Add 2-mercaptobenzothiazole, be heated to 50-60 DEG C；Benzothiazolyl thioacetyl galactose is obtained through post processing；
B) potassium hydroxide and benzothiazolyl thioacetyl galactose are added in benzyl chloride be heated to back flow reaction complete, reaction
Lower the temperature after completing, obtain benzothiazolyl sulfur for tetrabenzyl galactose through post processing；
C) being added in acetone dissolve for tetrabenzyl galactose by benzothiazolyl sulfur, add water, teeter chamber's warming middle-JIAO adds N-bromo
Succimide, stirs 0.5 hour, has reacted and obtained 2 through post processing, 3,4,6-tetra--oxygen-benzyl-D-galactopyranose；
Acetic anhydride in described step a: catalyst: galactose: the mol ratio of 2-mercaptobenzothiazole is 5.5:2:1:1.1；
Benzothiazolyl thioacetyl galactose in step b: benzyl chloride: the mol ratio of potassium hydroxide is 1:10-15: 4-8；
In step c, benzothiazolyl sulfur is 1:1.1-1.3 for the mol ratio of tetrabenzyl galactose Yu N-bromo-succinimide；
Catalyst is more than one in zinc chloride, iron chloride, zirconium chloride and aluminum chloride；
In step a, the response time is 24-30 hour, and in step b, the response time is 4-7 hour；
In step a, post processing is cancellation, extraction, and washing concentrates, adds organic solvent crystallization；
In step b, post processing is for go out with shrend, is extracted with ethyl acetate, and through 3 washings, is concentrated to dryness, adds mixed solvent
Crystallize；
Adding the sodium carbonate liquor of 5% after post processing is in step c, separate organic layer, aqueous layer with ethyl acetate extracts, and has separated
Machine phase, through concentrating, adds mixed solvent crystallize.
Preparation method the most according to claim 1, it is characterised in that in step c, mixed solvent be mol ratio be 2:2-3's
The mixing solvent of t-butyl methyl ether and isohexane.
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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 |
-
2013
- 2013-12-12 CN CN201310671212.8A patent/CN103694290B/en active Active
Patent Citations (4)
| 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 |
| 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 |
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| Impact of glycosylation on physicoechemical and biological properties of nitrification inhibitors;Daniele Pro，等;《Tetrahedron》;20120621;第68卷;7095-7102 * |
| 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);1227-1230 * |
| Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents;Xin-Shan Ye，等;《J. Med. Chem.》;20050504;第48卷(第11期);3688-3691 * |
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