Fiber polysaccharide polyester and preparation method thereof

Abstract

The invention discloses fiber polysaccharide polyester and a preparation method thereof, and belongs to the technical field of organic synthesis. The synthesis of cellobiose octaester and cellotriose undecanoate is carried out based on the characteristic that acetyl can generate directional migration in an acid environment, the whole process is mild in reaction condition and simple in treatment, required medicines are cheap and easy to obtain, intermediate products are synthesized by adopting a one-pot method, and the synthesis cost is low. Few intermediate products need to be separated and purified by silica gel column chromatography, so that the operation time of subsequent experimental treatment and separation and purification is saved, and the time of the whole reaction process is greatly shortened; and moreover, as repeated purification is not needed, the final yield is ensured.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a cellulose polysaccharide polyester and a preparation method thereof. Background Art

[0002] Cellulose is the main structural polysaccharide in plant cell walls, composed of β-D-glucose units connected by β-1,4-glycosidic bonds. In the process of cellulose decomposition, cellobiose and cellotriose are important intermediates, which are composed of two and three glucose units and have many potential applications, such as the preparation of biofuels and biomedicine.

[0003] As chemical derivatives of cellulose hydrolysate, cellobiose octaacetate and cellotriose undecaacetate have important research value and broad application prospects in the field of organic synthesis. They are derivatives obtained by acetylating cellobiose and cellotriose. These compounds not only have potential applications in the field of biomedicine, but also show diverse functionality and application potential in materials science and biotechnology. These carbohydrate compounds have potential application prospects in drug delivery systems, especially cellobiose, which has a simple structure and is suitable for drug packaging and delivery systems, providing support for the effective delivery of therapeutic drugs. Cellobiose and cellotriose can also be used as raw materials for biodegradable materials, used to prepare environmentally friendly materials and packaging materials, and play specific functions in coatings and composite materials. Summary of the invention

[0004] In view of the above-mentioned prior art, the present invention provides a cellulose polysaccharide polyester and a preparation method thereof to solve the technical problem of the difficulty in synthesizing cellulose polysaccharide polyester.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is: to provide a method for preparing cellulose polysaccharide polyester, comprising the following steps: S1: Install a protecting group on the 6-hydroxyl group of glucose to obtain a system comprising compound I, ; S2: performing an acetylation reaction on the system containing compound I to obtain compound II, ; S3: Selectively expose the 4-hydroxyl group of compound II to obtain compound III. ; S4: Compound III and 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate are dissolved in an organic solvent, stirred at -30 to -40°C for 5 to 15 minutes, then 4A molecular sieves are added in an inert gas atmosphere, stirred at -40°C for 5 to 10 minutes, trimethylsilyl trifluoromethanesulfonate is added, stirred at -40°C for 0.5 to 2 hours, and then separated and purified to obtain cellobiose octaester as shown in formula IV. ; S5: removing the acetyl group at position 1 of cellobiose octaester, and then reacting with trichloroacetonitrile and a catalyst in a solvent under the protection of an inert gas to generate 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate as shown in formula V, ; S6: 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate and compound III are co-dissolved in an organic solvent, stirred at -30~-40°C for 5~15 min, then 4A molecular sieves are added in an inert gas atmosphere, and the stirring reaction is continued at -40°C for 5~10 min, and then trimethylsilyl trifluoromethanesulfonate is added, and the stirring reaction is continued at -40°C for 0.5~2 h, and then separated and purified to obtain cellotriose undecyl ester as shown in formula VI. .

[0006] Based on the above technical solution, the present invention can also be improved as follows.

[0007] Further, the method for installing a protecting group on the 6-hydroxyl group of glucose in S1 is: Dissolve glucose in pyridine, add triphenylmethane at room temperature, then heat to 45-55°C and react overnight to obtain the product; the molar ratio of glucose to triphenylmethane is 1:1-3.

[0008] Further, the acetylation reaction of the system containing compound I in S2 comprises the following steps: Add acetic anhydride to the system containing compound I, then heat to room temperature, keep warm and stir to react for 30min~60min, then remove unreacted acetic anhydride, and then extract, concentrate and purify to obtain compound II; the molar ratio of acetic anhydride to glucose is 10~15:1.

[0009] Further, the preparation method of compound III in S3 comprises the following steps: Compound II is dissolved in an organic solvent, and then an acidifier is added, reacted at room temperature for 30 minutes, and then extracted, concentrated, and purified to obtain compound III; the acidifier is p-toluenesulfonic acid monohydrate, p-nitrobenzenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid, and the molar ratio of the acidifier to compound II is 1:10; the organic solvent is dichloromethane, methanol, toluene, acetonitrile, tetrahydrofuran or acetone.

[0010] Further, 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate is prepared by the following steps: A. Dissolve fully acetylated glucose in tetrahydrofuran, then add benzylamine to the resulting solution and react at room temperature for 1-2 hours to obtain product 1; B. Dissolve the product in dichloromethane, then add potassium carbonate at room temperature, stir at room temperature for 5 min~10 min, then add trichloroacetonitrile, and react at room temperature for 1~3 h to obtain; the molar ratio of fully acetylated glucose, benzylamine, potassium carbonate and trichloroacetonitrile is 1:1~2:2:3~5.

[0011] Furthermore, in S4, the molar ratio of compound III, 2,3,4,6-tetra-O-acetyl-α / β-pyranoglucopyranosyl trichloroacetimidate and trimethylsilyl trifluoromethylsulfonate is 1.7-1.8:2-3:0.2-0.3.

[0012] Further, 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate is prepared by the following steps: A. Dissolve cellobiose octaester in tetrahydrofuran, then add benzylamine to the resulting solution, react at room temperature for 1-2 hours, then extract and concentrate to obtain an intermediate product; B. Dissolve the intermediate product in dichloromethane, then add potassium carbonate at room temperature, stir at room temperature for 5 min to 10 min, then add trichloroacetonitrile, react at room temperature for 1 to 3 h to obtain the product.

[0013] Furthermore, the molar ratio of cellobiose octaester, benzylamine, potassium carbonate and trichloroacetonitrile is 1:1~2:1.5~2:3~5.

[0014] Furthermore, in S6, the molar ratio of 2,3,6,2',3'4'6'-heptadeca-O-acetyl-α / β-pyranoglucopyranosyl trichloroacetimidate, compound III and trimethylsilyl trifluoromethylsulfonate is 1.7-1.8:2-3:0.2-0.3.

[0015] The invention also discloses the cellulose polysaccharide polyester prepared by the preparation method.

[0016] The beneficial effects of the present invention are as follows: the synthesis of cellobiose octaester and cellotriose undecanedeester in the present invention is based on the characteristic that the acetyl group will undergo directional migration in an acidic environment, the reaction conditions of the whole process are mild, the treatment is simple, the required drugs are cheap and easy to obtain, the intermediate products are mostly synthesized by a one-pot method, and very few intermediate products need to be separated and purified by silica gel column chromatography, which saves the operation time of subsequent experimental treatment and separation and purification, and greatly shortens the time of the whole reaction process; and since multiple purifications are not required, the final yield is guaranteed. DETAILED DESCRIPTION

[0017] The specific implementation modes of the present invention are described in detail below with reference to the embodiments. Example

[0018] A method for preparing cellobiose octaester comprises the following steps: Synthesis of 1,2,3,6-tetra-O-acetyl-α / β-pyranose (Compound III), the reaction equation is as follows:

[0019] a) Glucose (10 g, 55.5 mmol) was dissolved in pyridine, and triphenylmethane (TrCl, 17.4 g, 62.4 mmol) was then added under stirring at room temperature, and the temperature was raised to 50° C. and stirred to react overnight to obtain a system containing compound I, which was directly carried out to the next step without treatment;

[0020] b) At 0°C, acetic anhydride (52.3 mL) was slowly added to the system containing compound I, and the temperature was raised to room temperature after the addition, and the reaction was kept warm for 50 minutes; then sodium bicarbonate powder was added to remove excess acetic anhydride, and then extracted and concentrated, and then separated and purified by silica gel column chromatography, the polarity of the eluent was: [V(PE):V(EA)=5:1], to obtain a transparent syrup compound II (27.4 g, 85%);

[0021] c) Compound II was dissolved in dichloromethane at room temperature, and a catalytic amount (10% molar equivalent) of p-toluenesulfonic acid monohydrate (TsOH·H2O) was added under stirring. The mixture was kept warm for 30 minutes. After extraction and concentration, the mixture was separated and purified by silica gel chromatography. The polarity of the eluent was [V(PE):V(EA)=2:1] to obtain a transparent syrup compound III (14.6 g, 88%).

[0022] The detection spectrum data of compound III is: 1 H NMR (600 MHz, CDCl3) d =5.69 (d,J = 8.2 Hz, 1H), 5.10 (t, J = 9.3Hz, 1H), 5.06 - 5.03 (m, 1H), 4.49- 4.46 (m, 1H), 4.29 (dd, J = 12.4, 2.2 Hz,1H), 3.66 (ddd, J = 10.0, 4.2, 2.2 Hz, 1H), 3.59 (dt, J = 9.3, 4.3 Hz, 1H), 2.11 (s, 3H), 2.09 (d, J = 5.0 Hz, 6H), 2.03 (s, 3H); 13 C NMR (151 MHz, CDCl3) d =171.94, 171.29, 169.66, 169.18, 91.93,89.44, 75.09, 70.37, 68.51, 62.62, 20.95, 20.91, 20.71, 20.61; HRMS (ESI m / z, MNa + ) calcd for C 14 H 20 O 10 Na 371.0954, found 371.0946. (2) Synthesis of 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate, the reaction equation is as follows:

[0023] a) Dissolve fully acetylated glucose (10 g, 25.6 mmol) in tetrahydrofuran, then add benzylamine (BnNH2, 4.2 mL, 38.4 mmol) under stirring at room temperature, and react at room temperature for 2 h. After the reaction is complete, extract and concentrate to obtain product 1; b) Product 1 was dissolved in dichloromethane at room temperature, and then potassium carbonate was added under stirring, and the mixture was stirred at room temperature for 10 min. Trichloroacetonitrile was then added, and the mixture was reacted at room temperature for 2 h. After extraction and concentration, the mixture was separated and purified by silica gel chromatography. The polarity of the eluent was [V(PE):V(EA)=6:1], and a transparent syrupy compound 1 (8.9 g, 71%) was obtained, namely 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate. The molar ratio of the added potassium carbonate and trichloroacetonitrile to the fully acetylated glucose was 2:4:1.

[0024] (3) Synthesis of 1,2,3,6-tetra-O-acetyl-α / β-pyranose-(4→1)-2,3,4,6-tetra-O-acetyl-α / β-pyranose (cellobiose octaester, structural formula shown in Formula IV)

[0025] 2,3,4,6-tetra-O-acetyl-α / β-pyranose trichloroacetimidate (8.9 g, 18.1 mmol) was dissolved in dichloromethane, and then compound III (5.3 g, 15.1 mmol) was added, and the mixture was stirred at -40°C for 10 min. Then, 0.5 g of 4A molecular sieve was added under nitrogen atmosphere, and the mixture was stirred at -40°C for 8 min. Then, trimethylsilyl trifluoromethylsulfonate (TMSOTf) (0.27 mL, 1.5 mmol) was slowly added, and the mixture was kept warm (-40°C) for 2 h after the addition. After the reaction was completed, triethylamine was added to quench the reaction, and the mixture was extracted and concentrated, and then separated and purified by silica gel chromatography, and the polarity of the eluent was [V(PE):V(EA)=3:2] to obtain a white solid product (8.7 g, 85%), namely cellobiose octaester.

[0026] The detection spectrum data of cellobiose octaester is: 1 H NMR (600 MHz, CDCl3) d =5.69 (d, J = 8.1 Hz, 1H), 5.53 (t, J = 9.8Hz, 1H), 5.45 (d, J = 3.6 Hz, 1H), 5.12 – 5.02 (m, 4H), 4.89 (dd, J = 10.2,3.6 Hz, 1H), 4.51 - 4.49 (m, 1H), 4.29 (dd, J = 12.5, 2.3 Hz, 1H), 4.12 (dd,J = 12.3, 2.2 Hz, 1H), 3.66 (ddd,J = 9.9, 4.1, 2.2 Hz, 1H), 3.58 (d, J = 9.6Hz, 1H), 3.22 (d, J = 27.2 Hz, 1H), 2.12 (s, 3H), 2.10 (s, 3H), 2.09 (s, 6H), 2.03 (s, 6H), 2.01 (s, 6H).; 13 C NMR (151 MHz, CDCl3) d =172.01, 171.31, 170.98, 170.34, 170.30,169.81, 169.67, 169.19, 91.96, 90.29, 75.21, 75.12, 71.20, 70.36, 69.98,68.61, 68.52, 67.36, 62.60, 62.09, 20.96, 20.92, 20.89, 20.85, 20.82, 20.76,20.72, 20.63.; HRMS (ESl m / z, MNa ＋ ) calcd for C 28 H 38 O 19 Na 701.1905, found 701.1899. Example

[0027] A method for preparing cellotriose undecyl ester comprises the following steps: (1) Synthesis of 2,3,6,2',3'4'6'-heptadeca-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate (Compound V), the reaction equation is as follows:

[0028] a) Dissolve cellobiose octaester (Compound IV, 8.7 g, 12.8 mmol) in tetrahydrofuran, then add benzylamine (BnNH2) (2.1 mL, 19.2 mmol) under stirring at room temperature, react at room temperature for 2 h, extract and concentrate after the reaction is complete to obtain an intermediate product; b) The intermediate product was dissolved in dichloromethane at room temperature, potassium carbonate (3.5 g, 25.2 mmol) was added with stirring at room temperature, the mixture was kept warm and stirred for 10 min, and then trichloroacetonitrile (4.3 mL, 53.5 mmol) was added. The mixture was reacted for 2 h in a nitrogen atmosphere at room temperature. After extraction and concentration, the mixture was separated and purified by silica gel chromatography. The polarity of the eluent was [V(PE):V(EA)=4:1] to obtain a transparent syrupy compound V (7.3 g, 73%), i.e., 2,3,6,2',3'4'6'-heptadeca-O-acetyl-α / β-pyranoglucopyranosyl trichloroacetimidate.

[0029] (2) Synthesis of 1,2,3,6-2',3',4',6'-2",3",4",6"-undecyl-O-acetyl-α / β-pyranose (cellotriose undecyl ester, the structural formula is shown in Formula VI), the reaction equation is as follows:

[0030] Compound V (7.3 g, 9.4 mmol) was dissolved in dichloromethane, and then compound III (2.7 g, 7.8 mmol) was added, and stirred at -40 ° C for 10 min, and then 0.3 g of 4A molecular sieve was added under nitrogen atmosphere, and stirred at -40 ° C for 8 min; then trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.14 mL, 0.8 mmol) was slowly added, and after the addition, the mixture was kept warm (-40 ° C) for 2 h. After the reaction was completed, triethylamine was added to quench the reaction, and the extraction and concentration were separated and purified by silica gel chromatography, and the polarity of the eluent was [V (PE): V (EA) = 1: 1], and a white solid product (4.5 g, 60%) was obtained, namely, cellotriose undecyl ester.

[0031] The detection spectrum data of cellotriose undecyl ester is: 1 H NMR (600 MHz, CDCl3) d = 6.22 (d, J = 3.6 Hz, 1H), 5.67 (d, J = 5.1Hz, 1H), 5.50 (d, J = 4.1 Hz, 1H), 5.18 - 5.15 (m, 1H), 5.13 (d, J = 9.3 Hz,1H), 5.11 - 5.09 (m, 1H), 5.09 -5.06 (m, 1H), 4.99 - 4.95 (m, 1H), 4.94 -4.91 (m, 1H), 4.64 (d, J = 8.1 Hz, 1H), 4.50 (d,J = 7.9 Hz, 1H), 4.46 (d, J = 12.2 Hz, 1H), 4.42 (dd, J = 12.5, 4.2 Hz, 1H), 4.24 (dd, J = 12.3, 4.3 Hz,1H), 4.14 - 4.08 (m, 2H), 4.07 - 4.02 (m, 2H), 3.79 (dd, J = 10.2, 3.6 Hz,1H), 3.68 - 3.64 (m, 1H), 3.57 (d, J = 9.5 Hz, 1H), 2.15 (s, 3H), 2.13 (s,3H), 2.09 (d, J = 3.5 Hz, 9H), 2.07 (s, 3H), 2.05 (s, 3H), 2.02 (d, J = 3.2Hz, 6H), 2.00 (d, J = 1.5 Hz, 6H).; 13 C NMR (151 MHz, CDCl3) d =170.88, 170.78, 170.61, 170.40, 170.37,169.56, 169.53, 169.51, 169.42, 169.34, 169.15, 102.29, 101.08, 97.33, 90.51,77.79, 73.13, 72.54, 72.09, 71.80, 71.48, 70.83, 69.23, 68.18, 67.87, 67.46,63.66, 61.87, 61.65, 61.46, 21.31, 21.19, 20.99, 20.94, 20.93, 20.85, 20.84,20.79, 20.72, 20.67.; HRMS (ESl m / z,MNa ＋ ) calcd for C 38 H 52 O 26 Na 947.2645, found 947.2646. Although the specific implementation of the present invention is described in detail in conjunction with the embodiments, it should not be understood as limiting the scope of protection of this patent. Within the scope described in the claims, various modifications and variations that can be made by those skilled in the art without creative work still fall within the scope of protection of this patent.

Claims

1. A method for preparing a cellulose polysaccharide polyester, characterized in that: The following steps are involved: S1: Install a protecting group on the 6-hydroxyl group of glucose to obtain a system comprising compound I, ； S2: performing an acetylation reaction on the system containing compound I to obtain compound II, ； S3: Selectively expose the 4-hydroxyl group of compound II to obtain compound III. ； S4: Compound III and 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate are dissolved in an organic solvent, stirred and reacted at -30~-40°C for 5~15min, then 4A molecular sieves are added in an inert gas atmosphere, stirred and reacted at -40°C for 5~10min, trimethylsilyl trifluoromethanesulfonate is added, stirred and reacted at -40°C for 0.5~2h, and then separated and purified to obtain cellobiose octaester as shown in formula IV. ； S5: removing the acetyl group at position 1 of cellobiose octaester, and then reacting with trichloroacetonitrile and a catalyst in a solvent under the protection of an inert gas to generate 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate as shown in formula V, ； S6: 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate and compound III are co-dissolved in an organic solvent, stirred at -30~-40°C for 5~15 min, then 4A molecular sieves are added in an inert gas atmosphere, and the stirring reaction is continued at -40°C for 5~10 min, and then trimethylsilyl trifluoromethanesulfonate is added, and the stirring reaction is continued at -40°C for 0.5~2 h, and then separated and purified to obtain cellotriose undecyl ester as shown in formula VI. 。 2. The preparation method according to claim 1, characterized in that: The method for installing a protecting group on the 6-hydroxyl group of glucose in S1 is: Dissolve glucose in pyridine, add triphenylmethane at room temperature, then heat to 45-55°C, and react overnight to obtain the product; the molar ratio of glucose to triphenylmethane is 1:1-3.

3. The preparation method according to claim 2, characterized in that: The acetylation reaction of the system containing compound I in S2 comprises the following steps: Add acetic anhydride to a system containing compound I, then heat to room temperature, keep warm and stir to react for 30min~60min, remove unreacted acetic anhydride, extract, concentrate and purify to obtain compound II; the molar ratio of acetic anhydride to glucose is 10~15:

1.

4. The preparation method according to claim 1, characterized in that: The preparation method of compound III in S3 comprises the following steps: Compound II is dissolved in an organic solvent, an acidifier is added, the reaction is carried out at room temperature for 30 minutes, and then the compound III is obtained by extraction, concentration and purification; the acidifier is p-toluenesulfonic acid monohydrate, p-nitrobenzenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid, and the molar ratio of the acidifier to compound II is 1:10; the organic solvent is dichloromethane, methanol, toluene, acetonitrile, tetrahydrofuran or acetone.

5. The preparation method according to claim 1, characterized in that: The 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate is prepared by the following steps: A. Dissolve fully acetylated glucose in tetrahydrofuran, then add benzylamine to the resulting solution and react at room temperature for 1-2 hours to obtain product 1; B. Dissolve the product in dichloromethane, then add potassium carbonate at room temperature, stir at room temperature for 5 min to 10 min, then add trichloroacetonitrile, and react at room temperature for 1 to 3 h to obtain; the molar ratio of the fully acetylated glucose, benzylamine, potassium carbonate and trichloroacetonitrile is 1:1 to 2:2:3 to 5.

6. The preparation method according to claim 1, characterized in that: The molar ratio of compound III, 2,3,4,6-tetra-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate and trimethylsilyl trifluoromethylsulfonate in S4 is 1.7~1.8:2~3:0.2~0.

3.

7. The preparation method according to claim 1, characterized in that: The 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate is prepared by the following steps: A. Dissolve cellobiose octaester in tetrahydrofuran, then add benzylamine to the resulting solution, react at room temperature for 1-2 hours, then extract and concentrate to obtain an intermediate product; B. Dissolve the intermediate product in dichloromethane, then add potassium carbonate at room temperature, stir at room temperature for 5 min to 10 min, then add trichloroacetonitrile, react at room temperature for 1 to 3 h to obtain the product.

8. The preparation method according to claim 7, characterized in that: The molar ratio of cellobiose octaester, benzylamine, potassium carbonate and trichloroacetonitrile is 1:1-2:1.5-2:3-5.

9. The preparation method according to claim 1, characterized in that: The molar ratio of 2,3,6,2',3'4'6'-hepta-O-acetyl-α / β-pyranose glucopyranosyl trichloroacetimidate, compound III and trimethylsilyl trifluoromethylsulfonate in S6 is 1.7~1.8:2~3:0.2~0.

3.

10. Cellulose polysaccharide polyester obtained by the preparation method according to any one of claims 1 to 9.

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