CN104744542A - Selective modification method of cane sugar primary hydroxyl - Google Patents
Selective modification method of cane sugar primary hydroxyl Download PDFInfo
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Abstract
The invention provides a selective modification method of cane sugar primary hydroxyl. The selective modification method comprises the following steps: firstly, performing full-benzylation on cane sugar, by taking the full-benzylated cane sugar as a substrate, adding dicobalt octacarbonyl and silane, and performing selective removal on primary hydroxyl; substituting primary hydroxyl by using triethyl-silyl so as to obtain cane sugar of which 6'-hydroxyl is protected by triethyl-silyl or cane sugar of which 6,6'-hydroxyl is protected by triethyl-silyl, further removing triethyl-silyl by using tetrabutyl ammonium fluoride so as to obtain cane sugar of which 6'-hydroxyl is free or cane sugar of which 6,6'-hydroxyl is free. Selective modification and successive modification on 6,6'-primary hydroxyl can be achieved, and the selective modification method is good in selectivity, gentle in reaction condition and high in product yield.
Description
Technical field
The invention belongs to technical field of chemistry, be specifically related to the selective modification method of a kind of sucrose uncle position hydroxyl.
Background technology
Sucrose is that occurring in nature holds facile lower molecular weight oligosaccharides most, and its chemical structural formula is
as organic material, it is cheap, purity is high, stable in properties, is therefore extensively subject to the favor of industry member; End modified (i.e. the chemically modified of uncle position hydroxyl) of sucrose is the most important research direction of sucrochemistry, but due to the structural complexity of sucrose, and it is end modified faces following two difficulties:
(1) sucrose has 3 uncles position hydroxyls (6,6 ', 1 ' position hydroxyl), sterically hindered comparatively large, active minimum due to 1 ' position hydroxyl, and activity difference between 6 ' position hydroxyl and 6 hydroxyls is less, the more difficult realization of selective modification; (2) sucrose glycosidic link very easily hydrolytic cleavage in acid condition, there are some researches show that the methanol hydrochloride solution of 0.1% can by sucrose complete hydrolysis in 30 minutes, the special sensitivity to acid of sucrose greatly limit the chemically modified to sucrose uncle position hydroxyl, still lacks effective means up to now to the selective modification of sucrose uncle position hydroxyl.
Summary of the invention
For solving the problem, the invention provides the selective modification method of a kind of sucrose uncle position hydroxyl, the method alternative is good, reaction conditions is gentle and product yield is high.
A selective modification method for sucrose uncle position hydroxyl, comprises the following steps:
(1) sucrose is dissolved in the first organic solvent, under alkaline environment, adds cylite or Benzyl Chloride, under room temperature, react 24h, after purifying, obtain octa-O-benzyl sucrose;
(2) octa-O-benzyl sucrose solution is obtained after being dissolved by described octa-O-benzyl sucrose; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; stirring reaction; remove 6 ' position benzyl or 6; the two benzyl in 6 ' position; after purifying, obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl.
Preferably; in step (2), described octa-O-benzyl sucrose is dissolved in toluene and obtains octa-O-benzyl sucrose solution; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; stirring reaction 18h is carried out at 50 ~ 55 DEG C; remove 6 ' position benzyl; after purifying; obtain the sucrose that 6 ' position hydroxyl is protected by triethyl silyl; the molar weight of described cobalt octacarbonyl is 1.5 times of described octa-O-benzyl sucrose molar weight, and the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
Preferably; in step (2), described octa-O-benzyl sucrose is dissolved in benzene and obtains octa-O-benzyl sucrose solution; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; heating reflux reaction 18h; remove 6; the two benzyl in 6 ' position; after purifying; obtain 6; the sucrose that 6 ' position hydroxyl is protected by triethyl silyl; the molar weight of described cobalt octacarbonyl is 3 times of described octa-O-benzyl sucrose molar weight, and the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
Preferably, described in described step (1), the first organic solvent is DMF or tetrahydrofuran (THF).
Preferably, the molar weight of cylite or Benzyl Chloride described in described step (1) is 9.6 ~ 16 times of described sucrose molar weight.
Preferably, described in step (2), the preparation method of the mixing solutions of cobalt octacarbonyl and triethyl silicane is: described cobalt octacarbonyl and triethyl silicane are mixed under carbon monoxide environment, stir until solution clarification, no longer produce bubble, obtain the mixing solutions of described cobalt octacarbonyl and triethyl silicane.
Preferably, the sucrose that described 6 ' position hydroxyl is protected by triethyl silyl is dissolved in tetrahydrofuran (THF), add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, remove triethyl silyl, after purifying, obtain the sucrose that 6 ' position hydroxyl is free, the sucrose that described 6 ' position hydroxyl is free carries out esterification, obtain the sucrose that 6 ' position hydroxyl is protected by alkyloyl, the sucrose that described 6 ' position hydroxyl is protected by alkyloyl is joined in the mixing solutions that cobalt octacarbonyl and triethyl silicane formed, at 65 ~ 75 DEG C of stirring reaction 18 ~ 24h, 6 ' position hydroxyl is obtained by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl after purifying, described 6 ' position hydroxyl is dissolved in tetrahydrofuran (THF) by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl, add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, remove triethyl silyl, obtain 6 ' position hydroxyl by the sucrose that alkyloyl is protected and 6 hydroxyls are free, the molar weight of described cobalt octacarbonyl is 6 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl, and the molar weight of described triethyl silicane is 20 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl.
Preferably, the molar weight of described tetrabutyl ammonium fluoride is 1.2 times of the sucrose molar weight that the sucrose protected by triethyl silyl of described 6 ' position hydroxyl or described 6 ' position hydroxyl are protected by alkyloyl and 6 hydroxyls are protected by triethyl silyl.
Preferably, the sucrose that described 6 ' position hydroxyl is free is dissolved in pyridine, then adds aceticanhydride, carries out esterification 3h, obtain the sucrose that 6 ' position hydroxyl is protected by ethanoyl.
Preferably, the molar weight of described aceticanhydride is 5 ~ 10 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates, and the molar weight of described pyridine is 10 ~ 20 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates.
First the present invention carries out entirely Benzylation to sucrose; then with full benzyl sucrose for substrate; add cobalt octacarbonyl and silane; carry out the selectively removing of uncle position benzyl; 6 ', 6 benzyls are replaced by triethyl silyl; obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, selectively removing 6 ', 6 benzyls.
Except above-mentioned selectively removing 6 ', 6 benzyl methods, also can realize sucrose 6 ', the priority of 6 benzyls removes, 6 ' position hydroxyl first be protected with by alkyloyl, then adds cobalt octacarbonyl and silane, 6 benzyls can be removed.Successively can introduce different functional groups at 6 ' position hydroxyl of sucrose and 6 hydroxyls like this, realize the orthogonally protect of 6 ' position hydroxyl and 6 hydroxyls, prepare more diversified sucrose derivative and sucrose material.
Reaction conditions of the present invention is gentle, the sucrose glycosidic link of acid labile can not have an impact, the fracture of sucrose glycosidic link not easily occurs.
To sum up, beneficial effect of the present invention comprises the following aspects:
(1) the modifying method selectivity of the present invention to sucrose uncle position hydroxyl is good, and product yield is high;
(2) reaction conditions of the present invention is gentle, can not the sucrose glycosidic link of acid labile have an impact.
Embodiment
The following stated is the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications are also considered as protection scope of the present invention.
A selective modification method for sucrose uncle position hydroxyl, comprises the following steps:
(1) sucrose is dissolved in the first organic solvent, under alkaline environment, adds cylite or Benzyl Chloride, under room temperature, react 24h, after purifying, obtain octa-O-benzyl sucrose;
(2) octa-O-benzyl sucrose solution is obtained after being dissolved by described octa-O-benzyl sucrose; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; stirring reaction; remove 6 ' position benzyl or 6; the two benzyl in 6 ' position; after purifying, obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl.
Described in step (1), the first organic solvent is DMF or tetrahydrofuran (THF).
Described in step (1), alkali is sodium hydride, and the molar weight of described alkali is 9.6 ~ 12 times of described sucrose molar weight.
The molar weight of cylite or Benzyl Chloride described in step (1) is 9.6 ~ 16 times of described sucrose molar weight.
Described purification process in step (1) is: obtain reaction solution after reaction terminates, after reaction solution is slowly dripped methyl alcohol cancellation reaction under ice bath, react again and excessive cylite or Benzyl Chloride were reacted away in 2 hours, remove the first organic solvent under reduced pressure and obtain resistates, described resistates is dissolved in ethyl acetate, filter with short silicagel column and obtain filtrate, concentrated after filtrate is merged, use column chromatography and obtain described octa-O-benzyl sucrose.
In step (2), described octa-O-benzyl sucrose is dissolved in toluene and obtains octa-O-benzyl sucrose solution; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; stirring reaction 18h is carried out at 50 ~ 55 DEG C; remove 6 ' position benzyl; after purifying; obtain the sucrose that 6 ' position hydroxyl is protected by triethyl silyl; the molar weight of described cobalt octacarbonyl is 1.5 times of described octa-O-benzyl sucrose molar weight, and the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
Described octa-O-benzyl sucrose obtains the octa-O-benzyl sucrose solution that concentration is 1mol/L after being dissolved in toluene.
In step (2), described octa-O-benzyl sucrose is dissolved in benzene and obtains octa-O-benzyl sucrose solution; described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; heating reflux reaction 18h; remove 6, the two benzyl in 6 ' position, after purifying; obtain 6; the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, the molar weight of described cobalt octacarbonyl is 3 times of described octa-O-benzyl sucrose molar weight, and the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
In chemical equation, Bn-is benzyl; TES-is triethyl silyl; Ac-is ethanoyl.
Described octa-O-benzyl sucrose obtains the octa-O-benzyl sucrose solution that concentration is 1mol/L after being dissolved in benzene.
Described in step (2), the preparation method of the mixing solutions of cobalt octacarbonyl and triethyl silicane is: described cobalt octacarbonyl and triethyl silicane are mixed under carbon monoxide environment, stir until solution clarification, no longer produce bubble, obtain the mixing solutions of described cobalt octacarbonyl and triethyl silicane.
Step (2) described purification process is: after reaction terminates; obtain reaction solution; appropriate pyridine is added in described reaction solution; then air bubbling is used 20 minutes; filter with silicagel column and obtain filtrate; filtrate is washed rear merging by ethyl acetate concentrate, then use column chromatography the sucrose or 6 obtaining 6 ' position hydroxyl and protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl.
The sucrose or 6 that the described 6 ' position hydroxyl obtained is protected by triethyl silyl; the sucrose that 6 ' position hydroxyl is protected by triethyl silyl; be dissolved in tetrahydrofuran (THF); adding tetrabutyl ammonium fluoride; react 30 minutes under room temperature; remove triethyl silyl, obtain the sucrose or 6 that 6 ' position hydroxyl is free, the sucrose that 6 ' position hydroxyl is free.
Described cobalt octacarbonyl consumption, the difference of the solvent species that octa-O-benzyl sucrose is dissolved in and temperature of reaction, can to 6 of sucrose, 6 ' uncle position hydroxyl carries out different modifications, obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, then triethyl silyl is removed, the sucrose or 6 that 6 ' position hydroxyl is free can be obtained, the sucrose that 6 ' position hydroxyl is free, hydroxyl free in sucrose can react with other chemical substances, the chemical group of needs can be introduced, provide the foundation for preparing required sucrose derivative.
The sucrose that described 6 ' position hydroxyl is protected by triethyl silyl is dissolved in tetrahydrofuran (THF), add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, reaction removes triethyl silyl, after purifying, obtain the sucrose that 6 ' position hydroxyl is free, the sucrose that described 6 ' position hydroxyl is free carries out esterification, obtain the sucrose that 6 ' position hydroxyl is protected by alkyloyl, the sucrose that described 6 ' position hydroxyl is protected by alkyloyl is joined the mixing solutions of cobalt octacarbonyl and triethyl silicane, at 65 ~ 75 DEG C of stirring reaction 18 ~ 24h, 6 ' position hydroxyl is obtained by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl after purifying, described 6 ' position hydroxyl is dissolved in tetrahydrofuran (THF) by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl, add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, remove triethyl silyl, obtain 6 ' position hydroxyl by the sucrose that alkyloyl is protected and 6 hydroxyls are free, the molar weight of described cobalt octacarbonyl is 6 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl, and the molar weight of described triethyl silicane is 20 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl.
After triethyl silyl in the sucrose protected described 6 ' position hydroxyl by triethyl silyl removes, obtain the sucrose that 6 ' position hydroxyl is free, then with alkyloyl protection 6 ' position hydroxyl, the mixing solutions joining cobalt octacarbonyl and triethyl silicane again reacts, obtain 6 ' position hydroxyl by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl, remove triethyl silyl again, obtain 6 ' position hydroxyl by the sucrose that alkyloyl is protected and 6 hydroxyls are free, at this moment 6 free hydroxyl groups can react with other materials, thus the chemical group needed is introduced at 6 hydroxyls, then the alkyloyl in sucrose on 6 ' position is being removed, different chemical groups is introduced again on 6 ' position, thus realize modifying with priority the orthogonally protect of 6 ' position hydroxyl and 6 hydroxyls, obtain more diversified sucrose derivative and sucrose material.
Described alkyloyl is acetyl or benzoyl base.
The sucrose that described 6 ' position hydroxyl is protected by triethyl silyl is dissolved in tetrahydrofuran (THF) to obtain concentration be the sucrose solution that the 6 ' position hydroxyl of 1mol/L is protected by triethyl silyl.
The molar weight of described tetrabutyl ammonium fluoride is 1.2 times of the sucrose molar weight that described 6 ' position hydroxyl is protected by triethyl silyl.
The molar weight of described tetrabutyl ammonium fluoride is 1.2 times of the sucrose molar weight that described 6 ' position hydroxyl is protected by alkyloyl and 6 hydroxyls are protected by triethyl silyl.
The sucrose that described 6 ' position hydroxyl is free is dissolved in pyridine, then adds aceticanhydride, carries out esterification 3h, obtain the sucrose that 6 ' position hydroxyl is protected by ethanoyl.
The molar weight of described aceticanhydride is 5 ~ 10 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates, and the molar weight of described pyridine is 10 ~ 20 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates.
First the present invention carries out entirely Benzylation to sucrose; then with full benzyl sucrose for substrate; then cobalt octacarbonyl and silane is added; carry out the selectively removing of uncle position benzyl; 6 ', 6 benzyls are replaced by triethyl silyl; obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl; the sucrose that 6 ' position hydroxyl is protected by triethyl silyl; the sucrose or 6 that 6 ' position hydroxyl is free can be obtained after using tetrabutyl ammonium fluoride (TBAF) triethyl silyl to be removed again; the sucrose that 6 ' position hydroxyl is free, selectively removing 6 ', 6 benzyls.The present invention also can realize sucrose 6 ', the priority of 6 benzyls removes, and method for first to be protected with alkyloyl by 6 ' position hydroxyl, then adds cobalt octacarbonyl and silane, can remove 6 benzyls.Successively can introduce different functional groups at 6 ' position hydroxyl of sucrose and 6 hydroxyls like this, realize the orthogonally protect of 6 ' position hydroxyl and 6 hydroxyls, prepare more diversified sucrose derivative and sucrose material.
In prior art to the yield of selective modification product of sucrose uncle position hydroxyl often all lower than 30%, and the yield of the product that modifying method of the present invention obtains reaches 85%, and product yield is high.
The modified outcome obtained in prior art often on sucrose different loci be substituted thus obtain mixture, cause target product separation and purification difficulty, and the product that present method obtains is the pure substance of single structure, is easy to separation and purification to obtain target product.
Silylation protecting group (as triethyl silyl) in the silylation substitution product that present method generates is easy to remove and transform.
The priority that present method can realize sucrose 6 ' position benzyl and 6 benzyls removes, with realize they 6 ' and the orthogonally protect of 6 hydroxyls, prepare more diversified sucrose functional materials.
Present method mild condition, can not the sucrose glycosidic link of acid labile impact.
Below in conjunction with specific embodiment, specific implementation of the present invention is described in detail.
Embodiment one
(1) sucrose is dissolved in anhydrous N, after dinethylformamide (DMF), slowly add the sodium hydride that molar weight is sucrose molar weight 9.6 times, stirred at ambient temperature is after 30 minutes, slow dropping molar weight is the cylite of sucrose molar weight 9.6 times, 24h is reacted under room temperature, after monitoring reaction terminates, obtain reaction solution, after ice bath downhill reaction liquid slowly drips methyl alcohol cancellation reaction, react again and excessive cylite was reacted away in 2 hours, remove DMF under reduced pressure and obtain resistates, resistates is dissolved in ethyl acetate, filter out insolubles with short silicagel column and obtain filtrate, filtrate is merged concentrated rear directly column chromatography for separation, obtain product and octa-O-benzyl sucrose, the yield 75% of octa-O-benzyl sucrose, reaction equation is:
The nuclear magnetic data of product is:
1h NMR (400 megahertzes, deuterochloroform) δ 7.18-7.30 (m, 40H), 7.13-7.15 (m, 2H), 5.72 (d, 1H, J=3.5Hz), 4.87 (d, 1H, J=10.9Hz), 4.80 (d, 1H, J=10.9Hz), 4.70 (d, 1H, J=10.9Hz), 4.61-4.68 (m, 2H), 4.33-4.58 (m, 13H), 4.17-4.21 (t, 1H, J=7.3Hz), 4.06-4.14 (m, 2H), 4.91-4.96 (t, 1H, J=9.3Hz), 3.63-3.76 (m, 4H), 3.48-3.56 (m, 3H), 3.36-3.99 (dd, 1H, J=10.5, 1.2Hz).
13c NMR (100 megahertzes, deuterochloroform) 139.1,138.8,138.5,138.4,138.3,138.3,138.2,138.1,128.4,128.1,128.0,127.9,127.8,127.7,127.6,104.7,90.1,84.0,82.5,82.1,80.0,75.6,74.9,73.5,73.3,73.1,72.6,72.3,71.5,68.6;
(2) cobalt octacarbonyl is mixed under carbon monoxide environment with triethyl silicane, stir until solution clarification, no longer produce the mixing solutions that bubble obtains cobalt octacarbonyl and triethyl silicane, the octa-O-benzyl sucrose that step (1) obtains is dissolved in dry toluene and obtains the octa-O-benzyl sucrose solution that concentration is 1mol/L, after removing air, octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, stirring reaction 18h at 50 DEG C, remove 6 ' position benzyl, the molar weight of cobalt octacarbonyl is 1.5 times of octa-O-benzyl sucrose molar weight, the molar weight of triethyl silicane is 10 times of octa-O-benzyl sucrose molar weight.After monitoring reaction terminates; obtain reaction solution; add appropriate pyridine to be oxidized; then air bubbling is used 20 minutes; filtered by reaction solution silicagel column and obtain filtrate, filtrate is concentrated with merging after ethyl acetate washing, then column chromatography for separation; obtain the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, yield is 85%.
Reaction equation is:
Product nuclear magnetic data is:
1h NMR (400 megahertzes, deuterochloroform) δ 7.22-7.31 (m, 34H), 7.12-7.14 (m, 2H), 5.80 (d, 1H, J=3.6Hz), 4.92 (d, 1H, J=10.8Hz), 4.81 (d, 1H, J=10.9Hz), 4.73 (d, 1H, J=10.8Hz), 4.65 (d, 1H, J=11.5Hz), 4.64 (d, 1H, J=11.3Hz), 4.35-4.59 (m, 10H), 4.22 (t, 1H, J=6.9Hz), 4.04 (d, 1H, J=10.0Hz), 3.98 (dd, 1H, J=12.0, 5.7Hz), 3.92 (t, 1H, J=9.3Hz), 3.84 (d, 2H, J=5.6Hz), 3.77 (d, 1H, J=11.0Hz), 3.65 (t, 1H, J=9.6Hz), 3.50-3.58 (m, 3H), 3.41 (dd, 1H, J=10.6, 1.3Hz), 0.93 (t, 9H, J=7.9Hz), 0.60 (q, 6H, J=8.0Hz).
13c NMR (100 megahertzes, deuterochloroform) δ 139.0,138.7,138.5,138.4,138.2,138.1,138.0,128.3,128.2,128.0,127.8,127.7,127.6,127.5,127.4,104.5,90.0,84.3,83.1,82.0,81.6,79.9,77.6,75.5,74.8,73.4,73.1,72.4,72.1,70.9,70.5,68.5,64.1,6.8,4.3.
Mass-spectrometric data C
67h
78o
11si [M+Na]
+theoretical value: 1109.5206. observed value: 1109.5186.
Embodiment two
The present embodiment step (1) is with the step (1) of embodiment one;
(2) octa-O-benzyl sucrose is dissolved in dry-out benzene obtains the octa-O-benzyl sucrose solution that concentration is 1mol/L, after removing air, octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, in stirred at reflux reaction 18h, remove 6, the two benzyl in 6 ' position, the molar weight of cobalt octacarbonyl is 3 times of octa-O-benzyl sucrose molar weight, the molar weight of triethyl silicane is 10 times of octa-O-benzyl sucrose molar weight, after monitoring reaction terminates, obtain reaction solution, add appropriate pyridine, then air bubbling is used 20 minutes, reaction solution silicagel column is filtered and obtains filtrate, filtrate is concentrated with merging after ethyl acetate washing, column chromatography for separation, obtain 6, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, yield is 90%.
Reaction equation is:
The nuclear magnetic data of product is:
1h NMR (400 megahertzes, deuterochloroform) δ 7.24-7.35 (m, 30H), 5.87 (d, 1H, J=3.6Hz), 4.91 (d, 1H, J=10.7Hz), 4.85 (d, 1H, J=11.0Hz), 4.74 (d, 1H, J=10.7Hz), 4.70 (d, 1H, J=11.3Hz), 4.58-4.66 (m, 5H), 4.42-4.54 (m, 4H), 4.29 (t, 1H, J=7.3Hz), 3.81-4.00 (m, 5H), 3.74 (d, 1H, J=11.0Hz), 3.59-3.71 (m, 2H), 3.45-3.55 (m, 3H), 0.90-0.97 (m, 18H), 0.51-0.65 (m, 12H).
13c NMR (100 megahertzes, deuterochloroform) δ 139.0,138.6,138.5,138.2,138.0,128.3,128.2,128.1,128.0,127.9,127.7,127.6,127.5,127.4,127.3,104.3,89.6,84.3,82.4,82.1,81.1,80.3,77.2,75.7,74.7,73.5,73.2,72.6,72.0,71.5,71.4,63.5,61.4,6.9,6.8,4.5,4.3.
Mass-spectrometric data C
66h
86o
11si
2[M+Na]
+theoretical value 1133.5601. observed value 1133.5613.
Embodiment three
The present embodiment step (1) (2) are with step (1) (2) of embodiment one;
(3) sucrose that 6 ' position hydroxyl is protected by triethyl silyl will be dissolved in tetrahydrofuran (THF), then the TBAF that molar weight is the sucrose molar weight 1.2 times that 6 ' position hydroxyl is protected by triethyl silyl is added, react 30 minutes under room temperature, remove triethyl silyl, after monitoring reaction terminates, direct for reaction solution evaporate to dryness is obtained residue, residue is dissolved in ethyl acetate, filter through silicagel column and obtain filtrate, filtrate evaporate to dryness obtains the free sucrose of 6 ' position hydroxyl, the sucrose that 6 ' position hydroxyl is free is dissolved in appropriate pyridine, add appropriate aceticanhydride, after esterification is about 3h, the molar weight of aceticanhydride is the sucrose molar weight that 6 ' position hydroxyl dissociates is 5 times, the molar weight of pyridine is the sucrose molar weight 10 times that 6 ' position hydroxyl dissociates, proper amount of methanol stopped reaction is added under ice bath, after reaction solution evaporate to dryness, carry out post separation again, obtain the sucrose that 6 ' position hydroxyl is protected by ethanoyl, yield is 90%.Reaction equation is:
Product nuclear magnetic data:
1h NMR (400 megahertzes, deuterochloroform) δ 7.23-7.32 (m, 34H), 7.11-7.14 (m, 2H), 5.65 (d, 1H, J=3.5Hz), 4.92 (d, 1H, J=10.9Hz), 4.81 (d, 1H, J=10.9Hz), 4.78 (d, 1H, J=11.0Hz), 4.25-4.65 (m, 14H), 4.07-4.14 (m, 3H), 3.96 (t, 1H, J=9.3Hz), 3.72 (d, 1H, J=11.0Hz), 3.64 (t, 1H, J=9.6Hz), 3.58 (dd, 1H, J=10.6, 3.3Hz), 3.51-3.55 (m, 2H), 3.46 (dd, 1H, J=10.5, 1.4Hz), 1.99 (s, 3H).
13c NMR (100 megahertzes, deuterochloroform) δ 170.6,138.8,138.4,138.2,138.0,137.9,137.8,137.7,128.3,128.2,127.9,127.8,127.7,127.6,127.5,127.4,104.5,90.0,83.6,82.0,81.8,79.6,78.2,77.6,75.4,74.8,73.3,72.8,72.5,72.4,70.8,70.6,68.3,65.2,20.7.
Mass-spectrometric data C
63h
66o
12[M+Na]
+theoretical value 1037.4447, observed value 1037.4454.
The sucrose that 6 ' position hydroxyl is protected by ethanoyl is dissolved in dry toluene to obtain concentration be the sucrose solution that the 6 ' position hydroxyl of 1mol/L is protected by ethanoyl; after removing air; this solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, in 70 DEG C of stirring reaction 18h.The molar weight of cobalt octacarbonyl is 6 times of the sucrose molar weight that 6 ' position hydroxyl is protected by ethanoyl; the molar weight of triethyl silicane is 20 times of the sucrose molar weight that 6 ' position hydroxyl is protected by ethanoyl; after monitoring reaction terminates; add appropriate pyridine; then air bubbling is used 20 minutes; reaction solution silicagel column is filtered; filtrate is washed by ethyl acetate; filtrate is merged concentrated rear column chromatography for separation; obtain 6 ' position hydroxyl by the sucrose that ethanoyl is protected and 6 hydroxyls are protected by triethyl silyl, yield is 70%.Reaction equation is:
Product nuclear magnetic data is:
1h NMR (400 megahertzes, deuterochloroform) δ 7.23-7.33 (m, 39H), 5.66 (d, 1H, J=3.5Hz), 4.93 (d, 1H, J=10.9Hz), 4.86 (d, 1H, J=10.9Hz), 4.80 (d, 1H, J=10.8Hz), 4.67 (d, 1H, J=3.2Hz), 4.57-4.65 (m, 6H), 4.54 (s, 1H), 4.51 (d, 2H, J=4.6Hz), 4.49 (d, 1H, J=4.4Hz), 4.45 (d, 1H, J=7.2Hz), 4.37 (d, 1H, J=12.0Hz), 4.30-4.31 (m, 2H), 4.10-4.17 (m, 2H), 3.91-4.00 (m, 3H), 3.65-3.72 (m, 3H), 3.47-3.60 (m, 4H), 1.99 (s, 3H), 0.91-0.95 (m, 9H), 0.53-0.61 (m, 6H).
13c NMR (100 megahertzes, deuterochloroform) δ 170.7,139.0,138.9,138.5,138.1,137.9,128.5,128.4,128.1,128.0,127.9,127.8,127.7,127.6,104.6,90.1,83.8,82.2,82.0,80.1,78.2,77.3,75.7,74.9,73.5,73.2,73.1,72.9,72.6,71.9,71.2,65.2,61.5,20.8,6.9,4.5.
Mass-spectrometric data C
62h
74o
12si [M+Na]
+theoretical value 1061.4842. observed value 1061.4858;
6 ' position hydroxyl is dissolved in tetrahydrofuran (THF) by the sucrose that ethanoyl is protected and 6 hydroxyls are protected by triethyl silyl; then to add molar weight be 6 ' position hydroxyl by ethanoyl protects and the tetrabutyl ammonium fluoride of molar weight 1.2 times of sucrose that 6 hydroxyls are protected by triethyl silyl; react 30 minutes under room temperature; remove triethyl silyl; after monitoring reaction terminates; direct for reaction solution evaporate to dryness is obtained residue; residue is separated with silicagel column after dissolving; obtain 6 ' position hydroxyl by the sucrose that ethanoyl is protected and 6 hydroxyls are free, yield is 100%.
Reaction equation is:
Product nuclear magnetic data is:
1h NMR (400 megahertzes, deuterochloroform) δ 7.24-7.34 (m, 33H), 5.60 (d, 1H, J=3.6Hz), 4.90 (d, 1H, J=10.9Hz), 4.84 (d, 1H, J=10.9Hz), 4.76 (d, 1H, J=10.9Hz), 4.65 (d, 1H, J=11.4Hz), 4.55-4.62 (m, 4H), 4.50-4.52 (t, 2H, J=4.4Hz), 4.47 (d, 1H, J=4.1Hz), 4.42 (d, 1H, J=7.0Hz), 4.33-4.39 (m, 2H), 4.17-4.21 (dd, 1H, J=12.0, 3.2Hz), 4.08-4.14 (m, 2H), 3.95-4.05 (m, 3H), 3.65-3.69 (m, 2H), 3.40-3.59 (m, 5H).
13c NMR (100 megahertzes, deuterochloroform) δ 170.9,138.8,138.3,138.1,137.9,137.8,137.7,128.4,128.1,128.0,127.9,127.8,127.7,127.6,104.7,89.8,83.5,81.8,81.5,79.8,78.0,77.8,77.2,75.6,75.0,73.4,72.9,72.7,72.6,71.7,71.2,64.9,62.1,20.8.
Mass-spectrometric data C
56h
60o
12[M+NH
4]
+theoretical value 942.4423. observed value 942.4421.
Embodiment four
(1) sucrose is dissolved in anhydrous N, after dinethylformamide (DMF), slowly add the sodium hydride that molar weight is sucrose molar weight 12 times, stirred at ambient temperature is after 30 minutes, slow dropping molar weight is the cylite of sucrose molar weight 16 times, 24h is reacted under room temperature, after monitoring reaction terminates, obtain reaction solution, after ice bath downhill reaction liquid slowly drips methyl alcohol cancellation reaction, react again and excessive cylite was reacted away in 2 hours, remove DMF under reduced pressure and obtain resistates, resistates is dissolved in ethyl acetate, filter out insolubles with short silicagel column and obtain filtrate, filtrate is merged concentrated rear directly column chromatography for separation, obtain product and octa-O-benzyl sucrose,
Reaction equation is:
(2) cobalt octacarbonyl is mixed under carbon monoxide environment with triethyl silicane, stir until solution clarification, no longer produce the mixing solutions that bubble obtains cobalt octacarbonyl and triethyl silicane, the octa-O-benzyl sucrose that step (1) obtains is dissolved in dry toluene and obtains the octa-O-benzyl sucrose solution that concentration is 1mol/L, after removing air, octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, stirring reaction 18h at 55 DEG C, remove 6 ' position benzyl, the molar weight of cobalt octacarbonyl is 1.5 times of octa-O-benzyl sucrose molar weight, the molar weight of triethyl silicane is 10 times of octa-O-benzyl sucrose molar weight.After monitoring reaction terminates; obtain reaction solution; add appropriate pyridine to be oxidized; then air bubbling is used 20 minutes; reaction solution silicagel column is filtered and obtains filtrate; filtrate is concentrated with merging after ethyl acetate washing, and then column chromatography for separation, obtains the sucrose that 6 ' position hydroxyl is protected by triethyl silyl.
Reaction equation is:
Embodiment five
The present embodiment step (1) (2) are with step (1) (2) of embodiment four;
(3) by being dissolved in tetrahydrofuran (THF), to obtain concentration be the sucrose solution that the 6 ' position hydroxyl of 1mol/L is protected by triethyl silyl to the sucrose protected by triethyl silyl by 6 ' position hydroxyl, then the TBAF that molar weight is the sucrose molar weight 1.2 times that 6 ' position hydroxyl is protected by triethyl silyl is added, react 30 minutes under room temperature, remove triethyl silyl, after monitoring reaction terminates, direct for reaction solution evaporate to dryness is obtained residue, residue is dissolved in ethyl acetate, filter through silicagel column and obtain filtrate, filtrate evaporate to dryness obtains the free sucrose of 6 ' position hydroxyl, the sucrose that 6 ' position hydroxyl is free is dissolved in appropriate pyridine, add appropriate aceticanhydride, after esterification is about 3h, the molar weight of aceticanhydride is the sucrose molar weight that 6 ' position hydroxyl dissociates is 10 times, the molar weight of pyridine is 20 times of the sucrose molar weight that 6 ' position hydroxyl dissociates, proper amount of methanol stopped reaction is added under ice bath, after reaction solution evaporate to dryness, carry out post separation again, obtain the sucrose that 6 ' position hydroxyl is protected by ethanoyl.Reaction equation is:
The sucrose that 6 ' position hydroxyl is protected by ethanoyl is dissolved in dry toluene to obtain concentration be the sucrose solution that the 6 ' position hydroxyl of 1mol/L is protected by ethanoyl; after removing air; this solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, in 75 DEG C of stirring reaction 24h.The molar weight of cobalt octacarbonyl is 6 times of the sucrose molar weight that 6 ' position hydroxyl is protected by ethanoyl, the molar weight of triethyl silicane is 20 times of the sucrose molar weight that 6 ' position hydroxyl is protected by ethanoyl, after monitoring reaction terminates, add appropriate pyridine, then use air bubbling 20 minutes, filtered by reaction solution silicagel column, filtrate is washed by ethyl acetate, filtrate is merged concentrated rear column chromatography for separation, obtain 6 ' position hydroxyl by the sucrose that ethanoyl is protected and 6 hydroxyls are protected by triethyl silyl; Reaction equation is:
6 ' position hydroxyl is dissolved in tetrahydrofuran (THF) by the sucrose that ethanoyl is protected and 6 hydroxyls are protected by triethyl silyl; then to add molar weight be 6 ' position hydroxyl by ethanoyl protects and the tetrabutyl ammonium fluoride of 1.2 times of sucrose molar weight that 6 hydroxyls are protected by triethyl silyl; react 30 minutes under room temperature; remove triethyl silyl; after monitoring reaction terminates; direct for reaction solution evaporate to dryness is obtained residue; be separated with silicagel column after residue dissolves, obtain 6 ' position hydroxyl by the sucrose that ethanoyl is protected and 6 hydroxyls are free.
Reaction equation is:
The above embodiment only have expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a selective modification method for sucrose uncle position hydroxyl, is characterized in that, comprise the following steps:
(1) sucrose is dissolved in the first organic solvent, under alkaline environment, adds cylite or Benzyl Chloride, under room temperature, react 24h, after purifying, obtain octa-O-benzyl sucrose;
(2) octa-O-benzyl sucrose solution is obtained after being dissolved by described octa-O-benzyl sucrose; then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane; stirring reaction; remove 6 ' position benzyl or 6; the two benzyl in 6 ' position; after purifying, obtain the sucrose or 6 that 6 ' position hydroxyl is protected by triethyl silyl, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl.
2. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, in step (2), described octa-O-benzyl sucrose is dissolved in toluene and obtains octa-O-benzyl sucrose solution, then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, stirring reaction 18h is carried out at 50 ~ 55 DEG C, remove 6 ' position benzyl, after purifying, obtain the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, the molar weight of described cobalt octacarbonyl is 1.5 times of described octa-O-benzyl sucrose molar weight, the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
3. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, in step (2), described octa-O-benzyl sucrose is dissolved in benzene and obtains octa-O-benzyl sucrose solution, then described octa-O-benzyl sucrose solution is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, heating reflux reaction 18h, remove 6, the two benzyl in 6 ' position, after purifying, obtain 6, the sucrose that 6 ' position hydroxyl is protected by triethyl silyl, the molar weight of described cobalt octacarbonyl is 3 times of described octa-O-benzyl sucrose molar weight, the molar weight of described triethyl silicane is 10 times of described octa-O-benzyl sucrose molar weight.
4. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, described in step (1), the first organic solvent is DMF or tetrahydrofuran (THF).
5. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, the molar weight of cylite or Benzyl Chloride described in step (1) is 9.6 ~ 16 times of described sucrose molar weight.
6. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, described in step (2), the preparation method of the mixing solutions of cobalt octacarbonyl and triethyl silicane is: described cobalt octacarbonyl and described triethyl silicane are mixed under carbon monoxide environment, stir until solution clarification, no longer produce bubble, obtain the mixing solutions of described cobalt octacarbonyl and triethyl silicane.
7. as claimed in claim 1 sucrose uncle position hydroxyl selective modification method, it is characterized in that, the sucrose that described 6 ' hydroxyl is protected by triethyl silyl is dissolved in tetrahydrofuran (THF), add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, reaction removes triethyl silyl, after purifying, obtain the sucrose that 6 ' hydroxyl is free, the sucrose that described 6 ' position hydroxyl is free carries out esterification, obtain the sucrose that 6 ' position hydroxyl is protected by alkyloyl, the sucrose that described 6 ' position hydroxyl is protected by alkyloyl is joined in the mixing solutions of cobalt octacarbonyl and triethyl silicane, stirring reaction 18 ~ 24h at 65 ~ 75 DEG C, 6 ' position hydroxyl is obtained by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl after purifying, described 6 ' position hydroxyl is dissolved in tetrahydrofuran (THF) by the sucrose that alkyloyl is protected and 6 hydroxyls are protected by triethyl silyl, add tetrabutyl ammonium fluoride, react 30 minutes under room temperature, remove triethyl silyl, obtain 6 ' position hydroxyl by the sucrose that alkyloyl is protected and 6 hydroxyls are free, the molar weight of described cobalt octacarbonyl is 6 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl, and the molar weight of described triethyl silicane is 20 times of the sucrose molar weight that 6 ' position hydroxyl is protected by alkyloyl.
8. as claimed in claim 7 sucrose uncle position hydroxyl selective modification method; it is characterized in that, the molar weight of described tetrabutyl ammonium fluoride is 1.2 times of the sucrose protected by triethyl silyl of described 6 ' position hydroxyl or described 6 ' position hydroxyl is protected by alkyloyl and 6 hydroxyls are protected by triethyl silyl sucrose molar weight.
9. the selective modification method of sucrose uncle position hydroxyl as claimed in claim 7, is characterized in that, be dissolved in pyridine, then add sucrose free for described 6 ' position hydroxyl aceticanhydride, carry out esterification 3h, obtain the sucrose that 6 ' position hydroxyl is protected by ethanoyl.
10. as claimed in claim 9 sucrose uncle position hydroxyl selective modification method, it is characterized in that, the molar weight of described aceticanhydride is 5 ~ 10 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates, and the molar weight of described pyridine is 10 ~ 20 times of the sucrose molar weight that described 6 ' position hydroxyl dissociates.
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Citations (2)
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|---|---|---|---|---|
| CN101775051A (en) * | 2010-01-07 | 2010-07-14 | 北京大学 | Method for regioselectively removing O-benzyl protective group of sugar |
| WO2010105851A1 (en) * | 2009-03-19 | 2010-09-23 | Helmholtz-Zentrum für Infektionsforschung GmbH | Probe compound for detecting and isolating enzymes and means and methods using the same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105851A1 (en) * | 2009-03-19 | 2010-09-23 | Helmholtz-Zentrum für Infektionsforschung GmbH | Probe compound for detecting and isolating enzymes and means and methods using the same |
| CN101775051A (en) * | 2010-01-07 | 2010-07-14 | 北京大学 | Method for regioselectively removing O-benzyl protective group of sugar |
Non-Patent Citations (1)
| Title |
|---|
| YUE-TAO ZHAO，等: "Synthesis of raffinose family oligosaccharides by regioselective de-O-benzylation with Co2(CO)8/Et3SiH/CO system", 《TETRAHEDRON》 * |
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