CN101747386B - Preparation method of hepatin acid ester - Google Patents
Preparation method of hepatin acid ester Download PDFInfo
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- CN101747386B CN101747386B CN 200810147709 CN200810147709A CN101747386B CN 101747386 B CN101747386 B CN 101747386B CN 200810147709 CN200810147709 CN 200810147709 CN 200810147709 A CN200810147709 A CN 200810147709A CN 101747386 B CN101747386 B CN 101747386B
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- acid ester
- bromo
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- hepatin
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- 0 CCOC(C)(OC12)O[C@]1OC(*)[C@](*)C2OC(C)=O Chemical compound CCOC(C)(OC12)O[C@]1OC(*)[C@](*)C2OC(C)=O 0.000 description 4
- AUVGRVGPAIFPSA-TZUIHXBYSA-N CC(OC)(OC1C2OC(C)=O)O[C@H]1OC(COC(C)=O)[C@@H]2OC(C)=O Chemical compound CC(OC)(OC1C2OC(C)=O)O[C@H]1OC(COC(C)=O)[C@@H]2OC(C)=O AUVGRVGPAIFPSA-TZUIHXBYSA-N 0.000 description 1
- CYAYKKUWALRRPA-IFQGYWFMSA-N CC(OCC([C@@H](C(C1OC(C)=O)OC(C)=O)OC(C)=O)O[C@@H]1Br)=O Chemical compound CC(OCC([C@@H](C(C1OC(C)=O)OC(C)=O)OC(C)=O)O[C@@H]1Br)=O CYAYKKUWALRRPA-IFQGYWFMSA-N 0.000 description 1
- WOZGYKWDLWNSIZ-IFQGYWFMSA-N CC(OCC([C@@H](C(C1OC(C)=O)OC(C)=O)OC(C)=O)O[C@@H]1I)=O Chemical compound CC(OCC([C@@H](C(C1OC(C)=O)OC(C)=O)OC(C)=O)O[C@@H]1I)=O WOZGYKWDLWNSIZ-IFQGYWFMSA-N 0.000 description 1
- NBWFYJVPTWVPKZ-ASPZOFLUSA-N C[C@@H](OC1C2OC(C)=O)O[C@H]1O[C@H](COC(C)=O)[C@H]2OC(C)=O Chemical compound C[C@@H](OC1C2OC(C)=O)O[C@H]1O[C@H](COC(C)=O)[C@H]2OC(C)=O NBWFYJVPTWVPKZ-ASPZOFLUSA-N 0.000 description 1
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Abstract
The invention belongs to the technical field of organic chemistry, in particular to a preparation method of hepatin acid ester, which comprises the following steps: dissolving bromo-sugar into acetylized PEG-400, adding anhydrous sodium acetate, alcohol or glycosyl receptor and a 4-molecular sieve; stirring and reacting at room temperature to obtain the hepatin acid ester; and obtaining a pure hepatin acid ester product by the analysis and the purification of silica gel column. The invention has the advantages of less pollution, low cost of raw materials, high reaction speed, high yield and the like.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to a kind of preparation method of hepatin acid ester.
Background technology
Ortho ester is a kind of very important intermediate in the organic synthesis, and in carbohydrate was synthetic, 1,2-ortho ester was widely used in the synthetic of oligosaccharides as saccharide donor.At present, the preparation method of ortho ester has a lot, and wherein the most classical a kind of method is with Tetrabutyl amonium bromide/tetrabutylammonium iodide, organic bases [s-collidine, 2,6-lutidine, Et
3N, (MeO)
2CHNMe
2] as catalyzer.As: (1) Tetrahedron Letters, 2003,44,7863.
(2)Journal?of?Organic?Chemistry，1994，59，6728。
Another kind method is with silver salt (Ag
2SO
4And Ag
2CO
3Deng) and organic bases [s-collidine, EtN (Pr-i)
2] as catalyzer.As: (3) Journal of Organic Chemistry, 1995,60 (13), 3942.
(4)Carbohydrate?Research，1985，144(1)，137。
Moreover be as catalyzer with KF.As: (5) Tetrahedron Letters, 2004,45,8847.
The method that also has is to make catalyzer with 2,6-lutidine, [bmim] PF
6Make solvent.As: (6) Synlett.2005,6,997.
The use that above method has organic bases or argent compound or organic solvent, and these chemical substances are big for environment pollution.Although the method environmental pollution that has is less, has reacted aftertreatment and not only operated inconvenience and cause the product loss larger.
Summary of the invention
The objective of the invention is for shortcoming big for environment pollution among the preparation method who solves hepatin acid ester, we provide a kind of pollute little, raw material is cheap, speed of reaction is fast, productive rate is high and the method for simple and effective glycogen biosynthesis acid esters.
The reaction process of preparation hepatin acid ester is as follows: with bromo sugar (2,3,4; 6-four-O-ethanoyl bromo Glucopyranose, 2,3,4; 6-four-O-ethanoyl bromo mannopyranose, 2; 3,4,6-, four-O-ethanoyl bromo galactopyranose, 2; 3; 4,6-, four-O-benzoyl bromo mannopyranose and the full acetylated pectinose of bromo) be dissolved among the acetylize PEG-400, add again anhydrous sodium acetate, alcohol (methyl alcohol, ethanol, vinylcarbinol, Virahol and benzylalcohol etc.) or glycosyl acceptor and
Stir under the molecular sieve, room temperature, reaction obtains hepatin acid ester.
R
1＝Ac，Bz
R
2=CH
3-, Et-, (CH
3)
2CH-, H
2C=CHCH
2-, PhCH
2-, glycosyl
R
3＝CH
3-，Ph-
Embodiment
In order further to understand summary of the invention of the present invention, Characteristic, enumerate following examples:
Embodiment 1: with 150mg 2,3,4,6-four-O-ethanoyl bromo Glucopyranose is dissolved among the 1.5mL acetylize PEG-400, adds 120mg anhydrous sodium acetate, 0.147mL methyl alcohol and 150mg again
Stir 7h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3: 2), obtain pure 3,4; 6-three-O-ethanoyl Glucopyranose-1,2-(methyl ortho ester) 119mg, productive rate is 90%.
Embodiment 2: with 150mg 2,3,4,6-four-O-ethanoyl bromo Glucopyranose is dissolved among the 1.5mL acetylize PEG-400, adds 30mg anhydrous sodium acetate, 0.147mL methyl alcohol and 150mg again
Stir 10h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3: 2), obtain pure 3,4; 6-three-O-ethanoyl Glucopyranose-1,2-(methyl ortho ester) 104mg, productive rate is 79%.
Embodiment 3: with 87mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 0.9mL acetylize PEG-400, adds 35mg anhydrous sodium acetate, 0.086mL methyl alcohol and 87mg again
Stir 6h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(methyl ortho ester) 68mg, productive rate is 89%.
Embodiment 4: with 140mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 1.4mL acetylize PEG-400, adds 56mg anhydrous sodium acetate, 0.2mL ethanol and 140mg again
Stir 8h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(ethyl ortho ester) 110mg, productive rate is 86%.
Embodiment 5: with 154mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 1.5mL acetylize PEG-400, adds 63mg anhydrous sodium acetate, 0.25mL vinylcarbinol and 154mg again
Stir 8h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(propenyl ortho ester) 116mg, productive rate is 80%.
Embodiment 6: with 65mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 0.65mL acetylize PEG-400, adds 27mg anhydrous sodium acetate, 0.12mL Virahol and 65mg again
Stir 8h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(sec.-propyl ortho ester) 41mg, productive rate is 67%.
Embodiment 7: with 185mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 1.9mL acetylize PEG-400, adds 74mg anhydrous sodium acetate, 0.26mL propiolic alcohol and 185mg again
Stir 7h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(proyl ortho ester) 132mg, productive rate is 76%.
Embodiment 8: with 72mg 2,3,4,6-four-O-ethanoyl bromo mannopyranose is dissolved among the 0.72mL acetylize PEG-400, adds 30mg anhydrous sodium acetate, 0.18mL benzylalcohol and 72mg again
Stir 9h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3,4; 6-three-O-ethanoyl mannopyranose-1,2-(benzyl ortho ester) 58mg, productive rate is 76%.
Embodiment 9: with 94mg 2,3,4,6-four-O-ethanoyl bromo galactopyranose is dissolved among the 0.94mL acetylize PEG-400, adds 38mg anhydrous sodium acetate, 0.093mL methyl alcohol and 94mg again
Stir 8h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl galactopyranose-1,2-(methyl ortho ester) 62mg, productive rate is 75%.
Embodiment 10: the full acetylated bromo pectinose of 120mg is dissolved among the 1.2mL acetylize PEG-400, adds 59mg anhydrous sodium acetate, 0.143mL methyl alcohol and 120mg again
Stir 6h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, washing twice concentrates by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtains pure full acetylated pectinose 1,2-(methyl ortho ester) 65mg, and productive rate is 63%.
Embodiment 11: with 144mg 2,3,4,6-four-O-benzoyl bromo mannopyranose is dissolved among the 1.4mL acetylize PEG-400, adds 72mg anhydrous sodium acetate, 0.089mL methyl alcohol and 144mg again
Stir 20h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:1), obtain pure 3,4; 6-three-O-benzoyl mannopyranose-1,2-(methyl ortho ester) 120mg, productive rate is 90%.
Embodiment 12: with 240mg 2,3,4, and 6-four-O-ethanoyl bromo Glucopyranose and 76mg1:2,3:4-two-O-isopropylidene-α-D-galactopyranose is dissolved among the 3mL acetylize PEG-400, adds 96mg anhydrous sodium acetate and 300mg again
Stir 12h under the molecular sieve, room temperature.After the TLC detection reaction is complete; add the ethyl acetate dilution; wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3,4; 6-three-O-ethanoyl-D-Glucopyranose-1; 2-(1:2,3:4-two-O-isopropylidene-α-D-galactopyranose base ortho ester) 145mg, productive rate is 84%.
Embodiment 13: with 89mg2, and 3,4,6-, four-O-benzoyl bromo mannopyranose and 50mg methyl-2,3,4-three-O-benzyl-alpha-D-glucopyranoside is dissolved among the 1.4mL acetylize PEG-400, adds 36mg anhydrous sodium acetate and 140mg again
Stir 15h under the molecular sieve, room temperature.After the TLC detection reaction is complete; add the ethyl acetate dilution; washing twice, concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 2:1), obtain pure 3; 4; 6-three-O-ethanoyl-D-mannopyranose-1,2-(methyl-2,3; 4-three-O-benzyl-alpha-D-Glucose glycosides base ortho ester) 74mg, productive rate is 86%.
Embodiment 14: with 150mg2,3,4,6-, four-O-ethanoyl bromo Glucopyranose is dissolved among the 1.5mL acetylize PEG-400, adds 120mg anhydrous sodium acetate, 0.08mL methyl alcohol and 150mg again
Stir 5h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl Glucopyranose-1,2-(methyl ortho ester) 95mg, productive rate is 70%.
Embodiment 15: with 150mg 2,3,4,6-four-O-ethanoyl bromo Glucopyranose is dissolved among the 0.75mL acetylize PEG-400, adds 120mg anhydrous sodium acetate, 0.147mL methyl alcohol and 150mg again
Stir 10h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl Glucopyranose-1,2-(methyl ortho ester) 108mg, productive rate is 82%.
Embodiment 16: with 150mg 2,3,4,6-four-O-ethanoyl bromo Glucopyranose is dissolved among the 2.25mL acetylize PEG-400, adds 120mg anhydrous sodium acetate, 0.147mL methyl alcohol and 150mg again
Stir 7h under the molecular sieve, room temperature.After the TLC detection reaction is complete, add the ethyl acetate dilution, wash twice; concentrated by silicagel column purifying (eluent is petrol ether/ethyl acetate 3:2), obtain pure 3,4; 6-three-O-ethanoyl Glucopyranose-1,2-(methyl ortho ester) 115mg, productive rate is 87%.
Top embodiment can make the present invention of those skilled in the art complete understanding, but does not limit the present invention in any way.
Claims (10)
1. the preparation method of a hepatin acid ester is characterized in that: bromo sugar is dissolved among the acetylize PEG-400, add again anhydrous sodium acetate, alcohol or glycosyl acceptor and
Molecular sieve, stirring reaction under the room temperature obtains hepatin acid ester, separates obtaining the hepatin acid ester sterling through purification by silica gel column chromatography; Its reaction process is as follows:
2. the preparation method of a hepatin acid ester, it is characterized in that: with 185mg2,3,4,6-, four-O-ethanoyl bromo mannopyranose is dissolved among the 1.9mL acetylize PEG-400, adds 74mg anhydrous sodium acetate, 0.26mL propiolic alcohol and 185mg again
Molecular sieve, stirring reaction 7h under the room temperature after the TLC detection reaction is complete, adds the ethyl acetate dilution; washing twice, concentrated by the silicagel column purifying, eluent is sherwood oil: ethyl acetate=3: 2 obtains pure 3; 4,6-, three-O-ethanoyl mannopyranose-1, the 2-propynyl ortho ester.
3. the preparation method of hepatin acid ester claimed in claim 1, it is characterized in that: described bromo sugar is benzoylation bromo sugar or acetylglycosyl bromide.
4. the preparation method of hepatin acid ester claimed in claim 3, it is characterized in that: described acetylglycosyl bromide is ethanoyl bromo Glucopyranose or ethanoyl bromo mannopyranose or ethanoyl bromo galactopyranose.
5. the preparation method of hepatin acid ester claimed in claim 3, it is characterized in that: described benzoylation bromo sugar is benzoyl bromo mannopyranose.
6. the preparation method of hepatin acid ester claimed in claim 1, it is characterized in that: described alcohol is methyl alcohol or ethanol or vinylcarbinol or Virahol or benzylalcohol.
7. the preparation method of hepatin acid ester claimed in claim 1, it is characterized in that: described glycosyl acceptor is monose.
8. the preparation method of hepatin acid ester claimed in claim 7, it is characterized in that: described monose is 1: 2,3: 4-two-O-isopropylidene-α-D-galactopyranose or methyl-2,3,4-three-O-benzyl-alpha-D-Glucose glycosides.
9. the preparation method of hepatin acid ester claimed in claim 1 is characterized in that: the mol ratio of bromo sugar, anhydrous sodium acetate and alcohol is: bromo sugar: anhydrous sodium acetate: alcohol=1: 1～4: 5～10; Bromo sugar,
The mass volume ratio g/mL of molecular sieve and acetylize PEG-400 is: bromo sugar:
Molecular sieve: acetylize PEG-400=1: 1: 5～15; Reacted under the room temperature 5～20 hours.
10. the preparation method of hepatin acid ester claimed in claim 1, it is characterized in that: the mol ratio of bromo sugar, glycosyl acceptor and anhydrous sodium acetate is: bromo sugar: glycosyl acceptor: anhydrous sodium acetate=1.5～2: 1: 2～4, bromo sugar,
The mass volume ratio g/mL of molecular sieve and acetylize PEG-400 is: bromo sugar:
Molecular sieve: acetylize PEG-400=1: 3: 15～45, reacted under the room temperature 10～20 hours.
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| CN 200810147709 CN101747386B (en) | 2008-11-28 | 2008-11-28 | Preparation method of hepatin acid ester |
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| CN101747386B true CN101747386B (en) | 2013-04-24 |
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| CN111672430B (en) * | 2020-06-04 | 2022-03-22 | 云南中烟工业有限责任公司 | Reversible phase-change atomized liquid gel containing alkyl-amido-glycosyl-arylidene four-section glycosyl gelling agent and preparation and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1242372A (en) * | 1998-07-17 | 2000-01-26 | 中国科学院生态环境研究中心 | Method for synthesizing disaccharide and trisaccharide ortho-esters |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1242372A (en) * | 1998-07-17 | 2000-01-26 | 中国科学院生态环境研究中心 | Method for synthesizing disaccharide and trisaccharide ortho-esters |
Non-Patent Citations (2)
| Title |
|---|
| N. K. KOCHETKOV, et al..A NEW METHOD OF GLYCOSYLATION.《tetrahedron》.1967,第23卷第693-707页. * |
| Shin-ichiro Shoda, et al..An environmentally benign and practical synthesis of sugar orthoesters promoted by potassium fluoride.《Tetrahedron Letters》.2004,第45卷第8847-8848页. * |
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