JP5155577B2 - Preparation of benzylated fructofuranose derivatives and benzylated aldose derivatives by acid hydrolysis of perbenzylated sucrose oligosaccharides - Google Patents

Description

  3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl by selective hydrolysis of fructofuranosyl bonds by acid hydrolysis of perbenzylated sucrose oligosaccharides of trisaccharides and higher ) -1,4,6-tri-O-benzyl-D-fructofuranose and 6-O- (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2 , 3,4-Tri-O-benzyl-D-glucopyranose, and benzylated D-fructofuranose derivatives and benzylated aldose derivatives.

  Sucrose oligosaccharides are more than trisaccharides in which aldohexose is added to glucose or fructofuranose constituting sucrose via glycoside bonds. Some sucrose oligosaccharides that have antioxidant activity, enzyme inhibitors and bifidobacteria activation are mass produced. It is possible to selectively hydrolyze only fructofuranosyl bonds without damaging glycosyl bonds other than fructofuranosyl bonds of perbenzylated sucrose oligosaccharides in which all hydroxyl groups of this sucrose oligosaccharide are protected with benzyl groups. If possible, it is possible to obtain a fructose derivative and an aldose derivative containing an oligosaccharide having a benzyl group or more. These sugar derivatives can be used as sugar acceptors and sugar donors that are important in carbohydrate chemistry, and are raw material intermediates for the production of new sucrose oligosaccharides, intermediates for the production of oligosaccharides as pharmaceuticals and agricultural chemicals, Is expected to be used as a raw material for synthesizing useful substrates in enzyme reactions.

By the way, perbenzylated sucrose in which all hydroxyl groups of sucrose consisting of disaccharides are benzylated is heated at 65 ° C. for 6 hours under the acidic condition of acetic acid-2M sulfuric acid, and 1,3,4,6-tetra-O— Although methods for producing monosaccharide derivatives of benzyl-D-fructofuranose and 2,3,4,6-tetra-O-benzyl-D-glucopyranose have been reported (Non-patent Document 1), The yield of 4,6-tetra-O-benzyl-D-fructofuranose is as low as 17%. In addition, when this reaction condition is applied to perbenzylated sucrose oligosaccharide, it is expected that the glycoside bond of aldohexose will also be cleaved.
RK Ness et al., `` 1,3,4,6-Tetra-O-benzyl-D-fructofuranose and some of its derivatives '', Carbohydrate Research, 1970, 13, p. 23.

  By selective acid hydrolysis of fructofuranosyl bonds by acid hydrolysis of perbenzylated sucrose oligosaccharides, 3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)- 1,4,6-tri-O-benzyl-D-fructofuranose and 6-O- (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2,3 , 4-tri-O-benzyl-D-glucopyranose, and benzylated D-fructofuranose derivatives and benzylated aldose derivatives containing oligosaccharides of two or more sugars are efficiently produced.

（Ｂｎはベンジル基を示す。）

（Ｂｎはベンジル基を示す。） As a result of diligent research in view of the above circumstances, the present inventors have selected perfrucylated sucrose oligosaccharides quickly and selectively only for fructofuranosyl bonds without damaging glycosyl bonds other than fructofuranosyl bonds under acidic conditions. Can be hydrolyzed to produce 3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D-full Cetofuranose and 6-O- (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2,3,4-tri-O-benzyl-D-glucopyranose, and The inventors have found that benzylated D-fructofuranose derivatives and benzylated aldose derivatives containing disaccharides or higher oligosaccharides can be obtained efficiently, and reached the present invention. That is, the present invention relates to benzylated D-fructofuranose derivatives and benzylated aldose derivatives containing oligosaccharides of disaccharides or more by selective hydrolysis of fructofuranosyl bonds of perbenzylated sucrose oligosaccharides of trisaccharides or more. Production method and 3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D-fructofuranose and 6-O -(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2,3,4-tri-O-benzyl-D-glucopyranose.

(Bn represents a benzyl group.)

(Bn represents a benzyl group.)

  The present invention provides sucrose oligosaccharides under mild conditions, as raw materials for producing oligosaccharides as pharmaceuticals and agricultural chemicals, and 3-O- (2,3,4,6-tetra-) expected as a useful substrate in enzyme reactions. O-benzyl-α-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D-fructofuranose and 6-O- (2,3,4,6-tetra-O-benzyl-α- D-galactopyranosyl) -2,3,4-tri-O-benzyl-D-glucopyranose, as well as benzylated D-fructofuranose derivatives and benzylated aldose derivatives containing disaccharides or higher oligosaccharides A useful method that can be manufactured well can be provided.

Hereinafter, the present invention will be described in detail.
The sucrose oligosaccharide used as a raw material of the present invention is more than a trisaccharide obtained by adding aldohexose with a glycosidic bond to glucose or fructofuranose constituting sucrose, and well-known ones can be used. Examples include raffinose, lactosucrose and melezitose.

  As the sucrose oligosaccharide, a perbenzylated sucrose oligosaccharide obtained by benzylating all sugar hydroxyl groups is used, and a well-known benzylation method can be used. For example, it can be obtained by a method using sodium hydride and benzyl bromide in dimethylformamide. It goes without saying that in addition to sodium hydride, benzyl chloride can be used in addition to potassium hydroxide, sodium hydroxide and benzyl bromide as the base.

  The acid hydrolysis reaction of perbenzylated sucrose oligosaccharide is preferably performed in the presence of an organic solvent. A known acid can be used as the acid, but sulfuric acid is preferably used. Although there is no restriction | limiting in particular about the density | concentration of sulfuric acid aqueous solution, Usually, it is used by 10% to 90% by volume percentage, Preferably, it is used at 50% to 90%. In particular, 75% is preferable.

  As the organic solvent, a known organic solvent can be used. For example, alcohol, dioxane, ether, benzene, toluene, dichloromethane, acetonitrile, tetrahydrofuran, dimethylformamide, and the like can be mentioned, but alcohol, dioxane, acetonitrile, and dimethylformamide that are highly miscible with water are preferably used. Is preferred. The mixing ratio of the acid aqueous solution and the organic solvent is not particularly limited, but is used in a volume ratio of 1: 100 to 1: 1, but preferably 1: 2 to 1:20.

  Although reaction temperature does not have a restriction | limiting in particular, Usually, it carries out at 0 to 60 degreeC. Preferably, it is the range of 10 degreeC-40 degreeC. The reaction time varies depending on the reaction temperature, the type of raw material, etc., but is in the range of several minutes to several hours.

  Purification is performed by a method used for normal sugar purification. For example, thin layer chromatography using silica gel or column chromatography can be used.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples.

[Example 1]
A perbenzylraffinose derivative (61.5 mg, 4.1 x 10 ^-2 mmol) was dissolved in dioxane (3.0 mL), 75% (v / v) sulfuric acid aqueous solution (0.3 mL) was added, and the mixture was stirred at room temperature for 60 minutes. Saturated aqueous sodium bicarbonate and ethyl acetate were added to extract the organic layer. The organic layer was dried over Na ₂ SO ₄ , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by column chromatography (developing solvent hexane: ethyl acetate = 4: 1 to 2: 1) to give 1,3,4,6-tetra-O-benzyl-D-fructofuranose (20.2 mg , Yield 91%) { ¹³ C-NMR (150 MHz, CDCl ₃ ) C-2β form δ 70.59, 71.89, 72.06, 72.65, 73.48, 73.56, 79.92, 83.40, 83.64, 102.42; C-2α form δ 70.05, 70.92, 71.82, 72.85, 73.24, 73.76, 81.74, 82.71, 86.33, 105.32} and 6-O- (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2, 3,4-tri-O-benzyl-D-glucopyranose (34.0 mg, yield 85%) { ¹³ C-NMR (150 MHz, CDCl ₃ ) C-1α form δ 67.59, 69.21, 69.49, 69.50, 70.69, 72.53, 72.95, 73.13, 73.36, 74.68, 74.97, 75.59, 76.66, 77.99, 78.43, 80.30, 81.75, 90.97, 98.36; C-1β form δ 67.78, 69.24, 72.92, 73.09, 73.48, 74.34, 74.65, 74.79, 74.86 , 75.10, 75.35, 76.63, 77.84, 78.67, 77.88, 83.47, 84.47, 97.16, 98.26} were obtained as oils.

[Example 2]
A perbenzyl lactosucrose derivative (109.9 mg, 7.4 x 10 ^-2 mmol) was dissolved in dioxane (3 mL), 75% (v / v) sulfuric acid aqueous solution (0.3 mL) was added, and the mixture was stirred at room temperature for 60 minutes. Saturated aqueous sodium hydrogen carbonate and ethyl acetate were added to extract the organic layer. The organic layer was dried over Na ₂ SO ₄ , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by column chromatography (hexane: ethyl acetate = 5: 1 to 3: 1) to give 1,3,4,6-tetra-O-benzyl-D-fructofuranose (35.6 mg, yield). (Rate 90%) { ¹³ C-NMR (150 MHz, CDCl ₃ ) C-2β form δ 70.59, 71.89, 72.06, 72.65, 73.48, 73.56, 79.92, 83.40, 83.64, 102.42; C-2α form δ 70.05, 70.92, 71.82, 72.85, 73.24, 73.76, 81.74, 82.71, 86.33, 105.32} and 4-O- (2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl) 2,3,6 -Tri-O-benzyl-D-glucopyranose (66.1 mg, yield 92%) { ¹³ C-NMR (150 MHz, CDCl ₃ ) C-1βδ 68.02, 68.12, 68.34, 72.56, 72.57, 73.07, 73.23, 73.59 , 74.87, 74.88, 75.11, 76.66, 77.35, 79.94, 82.54, 82.66, 82.82, 97.37, 102.81; C-1α δ 68.03, 68.21, 72.61, 73.08, 73.09, 73.15, 73.42, 73.65, 73.75, 74.70, 75.23, 75.28, 75.41, 76.40, 79.11, 79.95, 82.45, 91.44, 102.86} were obtained as oils.

[Example 3]
Perbenzylmergitose derivative (132.9 mg, 8.9 x 10 ^-2 mmol) was dissolved in dioxane (3 mL), 75% (v / v) aqueous sulfuric acid solution (0.3 mL) was added, and the mixture was stirred at room temperature for 6 hr. Saturated aqueous sodium hydrogen carbonate and ethyl acetate were added to extract the organic layer. The organic layer was dried over Na ₂ SO ₄ , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by thin layer chromatography (hexane: ethyl acetate = 4: 1) and 2,3,4,6-tetra-O-benzyl-D-glucopyranose (45.3 mg, 94% yield) { ¹³ C-NMR (150 MHz, CDCl ₃ ) C-1β form δ 70.59, 71.89, 72.06, 72.65, 73.48, 73.56, 79.92, 83.40, 83.64, 102.42; C-1α form δ 70.05, 70.92, 71.82, 72.85, 73.24, 73.76, 81.74, 82.71, 86.33, 105.32} and 2-O- (2,3,4,6-tetra-O-benzyl-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D -Fructofuranose (66.3 mg, Yield 77%) ( ¹³ C-NMR (150 MHz, CDCl ₃ ) C-2α form δ 68.26, 70.28, 70.83, 71.22, 71.73, 71.74, 73.05, 73.39, 73.44, 73.48, 75.00, 75.61, 77.60, 79.56, 79.78, 81.83, 84.43, 97.99, 102.54; C-2β form δ 70.43, 70.48, 70.86, 71.45, 71.46, 72.95, 73.08, 73.68, 74.90, 75.52, 77.36, 79.15, 81.04, 81.92 , 82.28, 82.55, 95.02, 105.68) as an oil.

  The present invention relates to a process for producing benzylated D-fructofuranose derivatives and benzylated aldose derivatives containing disaccharides or higher oligosaccharides by selective hydrolysis of fructofuranosyl bonds of perbenzylated sucrose oligosaccharides of trisaccharides or higher. And 3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D-fructofuranose and 6-O- ( 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2,3,4-tri-O-benzyl-D-glucopyranose. These sugar derivatives obtained by the present invention can be used as an important sugar acceptor or sugar donor in carbohydrate chemistry, and can be used as a raw material for producing a new sucrose oligosaccharide, a raw material for producing an oligosaccharide as a pharmaceutical or agrochemical, Furthermore, it is expected to be used for useful compounds in enzyme reactions.

Claims (5)

By acid hydrolysis reaction at room temperature using a Pabenjiru sucrose oligosaccharides 50% to 90% in an organic solvent (v / v) aqueous solution of sulfuric acid, is selectively acid hydrolysis fructofuranosyl bond, how to produce the benzylated D- fructofuranose derivatives and benzylation aldose derivatives. The method for producing a benzylated D-fructofuranose derivative and a benzylated aldose derivative according to claim 1 , wherein 75% (v / v) aqueous sulfuric acid solution is used in dioxane as the acid hydrolysis condition. The method for producing a benzylated D-fructofuranose derivative and a benzylated aldose derivative according to claim 1 or 2, wherein lactosucrose, raffinose or melezitose is used as the sucrose oligosaccharide. 3-O- (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) -1,4,6-tri-O-benzyl-D-fructo represented by the following formula (1) Furanose.

(Bn represents a benzyl group.) 6-O- (2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl) -2,3,4-tri-O-benzyl-D represented by the following formula (2) -Glucopyranose.

(Bn represents a benzyl group.)