CN102875610A - Method for preparing 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose - Google Patents
Method for preparing 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose Download PDFInfo
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- CN102875610A CN102875610A CN2012103465158A CN201210346515A CN102875610A CN 102875610 A CN102875610 A CN 102875610A CN 2012103465158 A CN2012103465158 A CN 2012103465158A CN 201210346515 A CN201210346515 A CN 201210346515A CN 102875610 A CN102875610 A CN 102875610A
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- triacetyl
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Abstract
The invention belongs to the technical field of chemical synthesis, and relates to a method for preparing 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose (compound I). The method comprises the following steps of: a, dissolving a raw material 2-acetamido-2-deoxidizing-1, 3, 4, 6-triacetyl-beta-D-pyranoglucose (compound III); uniformly agitating; adding thionyl chloride and acetic acid; b, agitating reaction mixture to carry out a reaction; c, filtering the reaction mixture; and d, distilling a solvent in a reduced pressure way; processing a rough product through a crystallizing solvent so as to obtain the 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose (compound I). According to the method provided by the invention, thionyl chloride-acetic acid is selected as a chlorinating agent, so that operation is safe and simple, and yield is high.
Description
Technical field
The invention belongs to chemosynthesis technical field, relate to preparation 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4, the method for 6-triacetyl-β-D-chloro pyranoglucose, this compound is used for the synthetic of glucosamine glucosides as organic synthesis intermediate.
Background technology
2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4,6-triacetyl-β-D-chloro pyranoglucose (Compound I) is the derivative of D-glucosamine, can be used as the required compound donator of synthesis of glycoside, is used for the synthetic of glucosaminide.
The preparation method of Compound I is disclosed among the patent US 5654412; the method is take D-Glucosamine Hydrochloride (Compound I I) as raw material; under sodium-acetate, diacetyl oxide and anhydrous hydrogen chloride gas effect, obtain Compound I through acylation reaction and chlorination reaction successively.At periodical Angewandte Chemie International Edition, 2012,51 (8), in the 1835-1839 page or leaf supporting document S-7 page or leaf, reported the method with sodium methylate, diacetyl oxide and Acetyl Chloride 98Min. and D-Glucosamine Hydrochloride reaction preparation Compound I (α-configurational isomer that comprises Compound I).
In the aforesaid method, use Acetyl Chloride 98Min. or anhydrous hydrogen chloride gas as chlorination reagent, operational danger is large, and speed of reaction is slow and productive rate is low.
Summary of the invention
The purpose of this invention is to provide a kind of with 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-1,3,4,6-triacetyl-β-D-Glucopyranose (compound III) is raw material, prepares 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4 take sulfur oxychloride-acetic acid as chlorizating agent, the method of 6-triacetyl-β-D-chloro pyranoglucose (Compound I), the method speed of reaction is fast, and process safety is easy, can improve content and the yield of product.The reaction formula of the method is as follows:
The preparation Compound I may further comprise the steps:
A, with organic solvent with raw material 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-1,3,4,6-triacetyl-β-D-Glucopyranose (compound III) dissolving stirs, and adds sulfur oxychloride and acetic acid;
B, the above-mentioned reaction mixture of stirring react;
C, reaction mixture is filtered;
D, underpressure distillation solvent, crude product obtains 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4 with recrystallisation solvent, 6-triacetyl-β-D-chloro pyranoglucose (Compound I).
It is characterized in that selected chlorizating agent is sulfur oxychloride-acetic acid.
In step a, the mol ratio of acetic acid and sulfur oxychloride is 0.1-3 in the chlorizating agent: 1, and the mol ratio of sulfur oxychloride and compound III is 1-6: 1, the sulfur oxychloride consumption is sluggish at least, and consumption is the aftertreatment trouble at most.
In step a, organic solvent is acetone, ether, tetrahydrofuran (THF), ethyl acetate, chloroform, methylene dichloride, acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide (DMSO) or toluene, and the preferred reaction solvent is methylene dichloride.
In step b, temperature of reaction is 0 ℃～60 ℃, 15 ℃～35 ℃ of preferable reaction temperature.
Method selective chlorination sulfoxide-acetic acid of the present invention is as chlorizating agent, and simple and safe operation and productive rate are high.The by product that reaction generates is volatile gases, easily absorbs and processes, and does not have other residues, so the easy separation and purification of product.Sulfur oxychloride and acetic acid are used, and also make the chlorination reaction of glucosamine C-1 position have stereoselectivity, can narrow spectrum generation beta configuration product.
Embodiment
Below pass through instance interpretation the present invention, but the present invention is not subjected to the restriction of these embodiment.
2-acetylaminohydroxyphenylarsonic acid 2-used in the present invention deoxidation-1,3,4,6-triacetyl-β-D-Glucopyranose (compound III) is according to periodical Australian Journal ofChemistry, 2004,1051-1053 page or leaf or chemical research and application 2003, the synthetic method preparation that the 573-574 page or leaf is described.
Embodiment 12-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4, the preparation of 6-triacetyl-β-D-chloro pyranoglucose (Compound I)
Compound III 20g and stirring are dissolved in the 150mL tetrahydrofuran (THF), add sulfur oxychloride 9.2g and acetic acid 1.5g.Said mixture filters 35 ℃ of reactions 8 hours, removes solvent under reduced pressure.Residuum filters with methylene dichloride-sherwood oil (1: 4) recrystallization, and the dry 15.6g white solid that gets is 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4,6-triacetyl-β-D-chloro pyranoglucose (Compound I), and productive rate 83%, 95～97 ℃ of mp,
1H NMR (CDCl
3) δ: 6.18 (d, 1H), 5.84 (d, 1H), (5.38-5.26 m, 1H), 5.21 (t, 1H), (4.53 ddd, 1H), 4.34-4.20 (m, 2H), 4.18-4.04 (m, 1H), (2.10 s, 3H), 2.05 (s, 6H), 1.98 (s, 3H).
Embodiment 22-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4, the preparation of 6-triacetyl-β-D-chloro pyranoglucose (Compound I)
Compound III 30g and stirring are dissolved in the 150mL methylene dichloride, add sulfur oxychloride 20.0g and acetic acid 8.0g.Said mixture filters 15 ℃ of reactions 12 hours, removes solvent under reduced pressure.Residuum filters with methylene dichloride-sherwood oil (1: 4) recrystallization, and the dry 21.9g white solid that gets is 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4,6-triacetyl-β-D-chloro pyranoglucose (Compound I), productive rate 78%.
Claims (3)
1. 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4, the preparation method of 6-triacetyl-β-D-chloro pyranoglucose (Compound I), its step comprises following:
A, with organic solvent with raw material 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-1,3,4,6-triacetyl-β-D-Glucopyranose (compound III) dissolving stirs, and adds sulfur oxychloride and acetic acid;
B, the above-mentioned reaction mixture of stirring react;
C, reaction mixture is filtered;
D, underpressure distillation solvent, crude product obtains 2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-3,4 with recrystallisation solvent, 6-triacetyl-β-D-chloro pyranoglucose (Compound I).
It is characterized in that selected chlorizating agent is sulfur oxychloride-acetic acid.
2. 2-acetylaminohydroxyphenylarsonic acid 2-according to claim 1 deoxidation-3,4,6-triacetyl-β-D-chloro pyranoglucose (Compound I) preparation method, it is characterized in that the mol ratio of acetic acid and sulfur oxychloride is 0.1-3 in the described chlorizating agent: 1, the mol ratio of sulfur oxychloride and compound III is 1-6: 1.
3. N-[4-according to claim 1 (4-(3-pyridyl)-1-imidazolyl) butyl] phthalimide (Compound I) preparation method, it is characterized in that described organic solvent is acetone, ether, tetrahydrofuran (THF), ethyl acetate, chloroform, methylene dichloride, acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide (DMSO) or toluene.Temperature of reaction is 0 ℃～60 ℃.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103465158A CN102875610A (en) | 2012-09-19 | 2012-09-19 | Method for preparing 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose |
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| CN2012103465158A CN102875610A (en) | 2012-09-19 | 2012-09-19 | Method for preparing 2-acetamido-2-deoxy-3, 4, 6-triacetyl-beta-D-chloro pyranoglucose |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996016071A1 (en) * | 1994-11-21 | 1996-05-30 | Glycomed, Inc. | PROCESSES FOR THE SYNTHESIS OF 3'-SUBSTITUTED LEWISx COMPOUNDS |
| US5654412A (en) * | 1996-05-29 | 1997-08-05 | Glycomed Incorporated | Processes for the synthesis of sialyl Lewisx compounds |
| WO1998004294A2 (en) * | 1996-07-26 | 1998-02-05 | Neorx Corporation | Radiolabeled annexins |
| WO2002094185A2 (en) * | 2001-05-18 | 2002-11-28 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
-
2012
- 2012-09-19 CN CN2012103465158A patent/CN102875610A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996016071A1 (en) * | 1994-11-21 | 1996-05-30 | Glycomed, Inc. | PROCESSES FOR THE SYNTHESIS OF 3'-SUBSTITUTED LEWISx COMPOUNDS |
| US5654412A (en) * | 1996-05-29 | 1997-08-05 | Glycomed Incorporated | Processes for the synthesis of sialyl Lewisx compounds |
| WO1998004294A2 (en) * | 1996-07-26 | 1998-02-05 | Neorx Corporation | Radiolabeled annexins |
| WO2002094185A2 (en) * | 2001-05-18 | 2002-11-28 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
Non-Patent Citations (3)
| Title |
|---|
| GORDON J.F. CHITTENDEN: ""Reaction of some 1,2-trans-aldose peracetates with thionyl chloride-acetic acid — a convenient synthesis of some 1,2-trans-per-O-acetyl-D-glycosyl chlorides"", 《CARBOHYDRATE RESEARCH》 * |
| JUSTIN M. CHALKER，ET AL.: ""Conversion of Cysteine into Dehydroalanine Enables Access to Synthetic Histones Bearing Diverse Post-Translational Modifications"", 《ANGEW. CHEM. INT. ED.》 * |
| YASUHIRO HORITA，ET AL.: ""Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives"", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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