CN103709212B - A kind of technique preparing 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose - Google Patents
A kind of technique preparing 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose Download PDFInfo
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- CN103709212B CN103709212B CN201310671228.9A CN201310671228A CN103709212B CN 103709212 B CN103709212 B CN 103709212B CN 201310671228 A CN201310671228 A CN 201310671228A CN 103709212 B CN103709212 B CN 103709212B
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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 one and prepare 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranosyl
The technique of sugar.
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, # 15p. 5993
5995, costly, cost is the highest for said method catalyst triphenyl Tetrafluoroboric acid carbon ratio, or uses galactose to carry out acetyl
Changing, then prepare p-methylphenyl thioacetyl galactose, through Benzylation, N-bromo-succinimide sloughs toluene-ω-thiol,
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, # 11p. 3,688 3691, use toxicity in this method stronger, and abnormal smells from the patient compares
Big 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 technique preparing 2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose.
The present invention is achieved by the following measures:
One prepares 2, the technique of 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 9 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 technique, described acetic anhydride: catalyst: galactose: the mol ratio of 2-mercaptobenzothiazole is 6.5: 2:1:
1.2
Described technique, benzothiazolyl thioacetyl galactose: benzyl chloride: the mol ratio of potassium hydroxide is 1:10-
15 :4-8。
Described technique, benzothiazolyl sulfur is 1 for the mol ratio of tetrabenzyl galactose Yu N-bromo-succinimide:
1.1-1.3。
Described technique, catalyst includes zinc chloride, iron chloride, zirconium chloride or aluminum chloride.
Described technique, in step a, the response time is 24-30 hour, and in step b, the response time is 4-7 hour.
Described technique, in step a, post processing is cancellation, extraction, and washing concentrates, adds organic solvent crystallization.
Described technique, 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 technique, 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 technique, in step a, described organic solvent is t-butyl methyl ether, methanol or ethanol.
In described processing 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 technique, 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: present invention process 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 6.5: 2: 1:1.2
A) room temperature adds 65mol acetic anhydride and 20mol aluminum chloride, adds 10mol galactose at 10-15 DEG C point 9 batches, has reacted
Cheng Hou, adds 12mol 2-mercaptobenzothiazole, is heated to 50-60 DEG C；8.9mol benzothiazolyl sulfur is obtained through post processing
For acetyl galactose.
B) 44.5mol potassium hydroxide and 8.9mol benzothiazolyl thioacetyl galactose are added to 106.8mol benzyl chloride
In be heated to backflow, after react cooling, obtain 8.25mol benzothiazolyl sulfur for tetrabenzyl galactose through post processing.
C) it is added in 40mol acetone dissolve for tetrabenzyl galactose by 8.25mol benzothiazolyl sulfur, adds 20mol water,
Teeter chamber's warming middle-JIAO adds 9.6mol N-bromo-succinimide, stirs 0.5 hour, has reacted and obtained through post processing
7.33mol2,3,4,6-tetra--oxygen-benzyl-D-galactopyranose, yield is 73.3%.
In step a, post processing is that the water of dropping 0-5 DEG C of 100mol stirs 2 hours, extracts extraction by the ethyl acetate of 50mol
Water intaking layer, separates organic facies 100mol water washing organic facies, separates organic facies and concentrate, add 10mol t-butyl methyl ether knot
Crystalline substance, filters, and is dried.
In step b, post processing is addition 50mol water in reaction system, stirs 30 minutes, by the ethyl acetate of 50mol
Extraction aqueous layer extracted, separates organic facies 50mol water washing organic facies, washs three times, separate organic facies and concentrate, be concentrated to dryness,
Add t-butyl methyl ether and the crystallize of 4mol isohexane of 2mol, filter, be dried.
Add the sodium carbonate liquor of 30mol 5% after post processing is in step c, separate organic layer, water layer 30mol acetic acid
Ethyl ester extracts, and separates organic facies, merges organic facies, washs with the water of 05mol, separates organic facies and concentrates, adds the tertiary fourth of 2mol
Ylmethyl ether and the crystallize of 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 9 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 (5)
1. prepare 2 for one kind, the technique 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 9 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 6.5:2:1:1.2；
Benzothiazolyl thioacetyl galactose in step b: benzyl chloride: the mol ratio of potassium hydroxide is 1:10-15: 4-8；
Described technique, catalyst is more than one in zinc chloride, iron chloride, zirconium chloride and aluminum chloride；
In step c, benzothiazolyl sulfur is 1:1.1-1.3 for the mol ratio of tetrabenzyl galactose Yu N-bromo-succinimide；
In step a, the response time is 24-30 hour, and in step b, the response time is 4-7 hour.
Technique the most according to claim 1, it is characterised in that in step a, post processing is cancellation, extraction, washing, concentrate, add
Enter organic solvent crystallization.
Technique the most according to claim 1, it is characterised in that in step b, post processing is for go out with shrend, extracts by ethyl acetate
Take, through 3 washings, be concentrated to dryness, add mixed solvent crystallize.
Technique the most according to claim 1, it is characterised in that add the sodium carbonate liquor of 5% after post processing is in step c,
Separating organic layer, aqueous layer with ethyl acetate extracts, and separates organic facies, through concentrating, adds mixed solvent crystallize.
Technique the most according to claim 4, it is characterised in that in step c, mixed solvent be mol ratio be the tertiary fourth of 2:2-3
Ylmethyl ether and the mixed solvent 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 |
-
2013
- 2013-12-12 CN CN201310671228.9A patent/CN103709212B/en active Active
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 |
|---|
| Impact of glycosylation on physicoechemical and biological properties of nitrification inhibitors;Daniele Pro，等;《Tetrahedron》;20120621;第68卷;第7097页方案1，第7098页右栏第3-4段 * |
| 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);图1，第1228页左栏倒数第2段至第1229页左栏第1段 * |
| Xin-Shan Ye，等.Synthetic Iminosugar Derivatives as New Potential Immunosuppressive Agents.《J. Med. Chem.》.2005,第48卷(第11期),第3688页方案1. * |
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Address after: Shengquan Industrial Park 250204 Shandong city of Ji'nan province Zhangqiu City Diao Town Industrial Development Zone Applicant after: CARBOTANG BIOTECH CO.,LTD. Address before: Shengquan Industrial Park 250204 Shandong city of Ji'nan province Zhangqiu City Diao Town Industrial Development Zone Applicant before: CARBOTANG LTD. |
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Address after: 250204 Diaozhen Street Chemical Industrial Park, Zhangqiu District, Jinan City, Shandong Province Patentee after: Jinan Carbotang Biotech Co.,Ltd. Address before: 250204 Shengquan Industrial Park, Diaozhen Industrial Development Zone, Zhangqiu City, Jinan City, Shandong Province Patentee before: CARBOTANG BIOTECH CO.,LTD. |