TW201945382A - Xylose derivatives and process for preparation thereof - Google Patents

Abstract

Disclosure of the present invention relates to a method for synthesis of a xylose derivative, which comprises protecting a xylose with a protective group, followed by incorporating to a halogen atom as a leaving group; removing the protective groups and using water-soluble ligands to carry out a Suzuki cross-couplings reaction with a palladium catalyst in a water solution. Ten new xylose derivatives as obtained by the method are also provided.

Description

Xylose derivative and preparation method thereof

The present invention relates to a new method for synthesizing a xylose derivative and a new xylose derivative prepared therefrom.

Green chemistry is defined as the environmentally friendly design of chemical products and processes. Its philosophy of chemical research and engineering encourages the development of products and procedures that minimize the use and generation of hazardous substances. Relevant examples include: reducing toxic waste, using renewable raw materials, conducting environmental conditions to reduce energy consumption, using smaller amounts of catalyst, and achieving high percentage recovery of catalysts, etc. Green chemistry seeks to reduce and avoid pollution at its source and applies it to biochemistry, organic chemistry, inorganic chemistry, physical chemistry, analytical chemistry, and even carbohydrate chemistry. Most commonly, it focuses on industrial applications, such as minimizing hazardous waste and maximizing efficiency.

Recently, the development of water-soluble homogeneous catalysts has contributed to economic green chemistry. Since water-soluble catalysts are easily separated from the organic phase, they avoid the use of organic solvents and are cost-effective and environmentally friendly. Generally, green chemical methods require the following characteristics: (1) the use of non-toxic catalysts and solvents; and (2) the use of renewable resources to synthesize chemical compounds.

In recent years, sugar chemistry has been widely accepted in medical applications, such as biomaterials and pharmaceutical synthesis. Sugars are used to treat cancer, diabetes, AIDS, influenza, bacterial infections and rheumatoid arthritis. Excellent research on carbohydrate vaccines has been performed in recent years. However, most carbohydrate drugs are derived from natural sources such as polysaccharides and glycosides from plants, animals, and microorganisms.

Xylose was the first sugar isolated from wood and was classified as a monosaccharide of aldopenoses. It is derived from hemicellulose, one of the main ingredients of biomass. It has been reported that acid-catalyzed degradation of hemicellulose produces furfural. In addition, since xylose does not contain calories, it can be used as a diet food. Xylose and xylose derivatives can be used in various fields. Specifically, xylose and its derivatives can be applied in the green chemical industry.

However, there is a need to develop economical and efficient methods to obtain various xylose derivatives via green chemical methods.

Therefore, the present invention provides a new method for synthesizing a xylose derivative in an aqueous phase and in the presence of an organometallic catalyst. Through this method, it is easy to modify xylose to obtain a new xylose derivative from nature. Due to the recyclable catalyst and the use of water as a solvent, the reaction is environmentally friendly and economical. Xylose can be modified to obtain various functional groups that can affect the organism and / or make it applicable to biological materials.

In one aspect, the invention provides xylose derivatives having the general formula I: Formula I, wherein m in (R) m is an integer from 1 to 4; R is CH ₃ , OCH ₃ , or a halogen atom.

In a specific embodiment of the present invention, the xylose derivative is one selected from the group consisting of: 2- (4'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 1); 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2); 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3); 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4); 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5); 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6); 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7); 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8); 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9); and 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piran-3,4,5-triol (Compound 10).

In another aspect, the present invention provides a method for synthesizing a xylose derivative according to the present invention. The method includes the steps of: protecting a xylose with a protecting group, and then incorporating a halogen atom as a leaving group; removing the protecting group and using a water-soluble ligand to perform a palladium catalyst in aqueous solution with Suzuki (Suzuki ) Cross-coupling reaction to synthesize the derivative.

In one embodiment of the present invention, the halogen atom is an iodine atom.

In one example of the present invention, the water-soluble ligand is recovered.

In one example of the present invention, the palladium catalyst is recovered.

In one example of the present invention, the palladium catalyst is PdCl ₂ (NH ₃ ) ₂ , and the water-soluble ligand is a cationic 2,2′-bipyridine ligand.

In one example of the present invention, the cationic 2,2'-bipyridine ligand is dissolved in water to form solution A; and PdCl ₂ (NH ₃ ) _{2 is} dissolved in water to form solution B; and the solution A is added to Solution B to produce a cloudy solution, which eventually became clear to obtain a water-soluble palladium catalyst.

In one embodiment of the present invention, the Suzuki cross-coupling reaction is performed at a temperature not higher than 100 ° C.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the singular forms "a" (a, an) and "the" include plural referents unless the content is specifically indicated otherwise. Thus, for example, reference to "the same" includes a plurality of such samples and equivalents thereof known to those skilled in the art.

As used herein, the term "halogen atom" refers to an atom selected from the group of the Periodic Table consisting of five chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and砈 (At).

The invention provides a method for synthesizing a xylose derivative in the presence of a water-soluble palladium catalyst in an aqueous phase, and provides a friendly and economical green chemical method for synthesizing a xylose derivative.

The technology and materials related to the present invention are described below.

Solvent purification

On a distillation apparatus under a nitrogen atmosphere, magnesium sulfate was added to dichloromethane in a distillation flask and the temperature was set at ~ 50 ° C. The distillate was collected in a flask containing dry molecular sieves.

Free of water and air

If the reaction is sensitive to water and air, all experimental processes including reaction, extraction, drying, concentration, and column chromatography must be performed in the absence of air in nitrogen conditions. Therefore, solvents and chemicals must be free of water and air before use, and liquids must be transferred using a syringe and a needle (Teflon). The solution was concentrated using a rotary vacuum concentrator and a vacuum motor.

Reaction scheme

According to the present invention, the overall reaction scheme in the method for synthesizing a xylose derivative is provided as follows:

Acetylation

In one example of the present invention, the acetylation reaction scheme is provided as follows:

A solution of 0.75 g of xylose (5 mmol), 2.84 mL (30 mmol) of acetic anhydride, and 2.04 g (30 mmol) of imidazole in 700 mL of dichloromethane was placed in an ice bath for 30 minutes, followed by stirring for 12 hours. The reaction was then quenched by adding methanol and stirring for 30 minutes on ice. The mixture was diluted with dichloromethane, adjusted to a neutral pH with HCl, and extracted with Et ₂ O. Acetylated xylose (1.50 g, 94%) was obtained as a white solid by common work-up and column chromatography.

Phenol derivative reaction

In one example of the present invention, the phenol-derived reaction scheme is provided as follows (Lee et al., CARBOHYDRATE CHEMISTRY . 20 (6): 503-506, 2001):

Under a nitrogen atmosphere, mix 1.59 g (5 mmol) of acetylated xylose, 1.29 g (7.5 mmol) of 4-bromophenol, 0.7 mL (5 mmol) of TEA, and 0.87 mL (12.5 mmol) of 30 mL. The solution in methyl chloride was stirred for 24 hours to convert 4-bromophenol to 4-iodophenol. The mixture was diluted with 20 mL of saturated aqueous NaHCO _{3 (aq)} and extracted with Et ₂ O (30 mL × 3). The product was obtained as a white solid (1.29 g, 54%) by common post-treatment and column chromatography.

Deacetylation reaction

In one example of the present invention, the deacetylation reaction scheme is provided as follows (Will et al., J. Phys CHEM. B , 103: 8067, 1999):

A solution of 0.478 g (1 mmol) of starting material and 0.33 g (6 mmol) of sodium methoxide in 20 mL of methanol was stirred at atmospheric pressure for 8 hours. The mixture was adjusted to a neutral pH by adding HCl, and then extracted with Et ₂ O (30 mL × 3). After common post-treatment and column chromatography, a white solid product was obtained (0.32 g, 91%).

cation 2,2- Synthesis of bipyridine ligand

In a specific embodiment of the present invention, the water-soluble ligand is a cationic 2,2-bipyridine ligand, which can be synthesized according to the following scheme (Xue et al., Carbohydrate Research 344: 1646-1653, 2009):

The following ligands can be used in the present invention: 4,4'-dicarboxy-2,2'-bipyridine: 4,4'-dimethoxycarbonyl-2,2'-bipyridine; 4,4 ' -Bis (hydroxymethyl) -2,2'-bipyridine: 4,4'-bis (bromomethyl) -2,2'-bipyridine; or a cationic 2,2'-bipyridine ligand.

Synthesis of the aforementioned ligands is provided below.

(1) 4,4'- Dicarboxyl -2,2'- Bipyridine Synthesis

The synthesis scheme of 4,4'-dicarboxy-2,2'-bipyridine is provided as follows:

4,4'-dimethyl-2,2'-bipyridine (5 g) was dissolved in 125 mL of H ₂ SO ₄ (98%). Add K ₂ Cr ₂ O ₇ and maintain the temperature between ~ 70-80 ° C. When the solution changed from yellow to black, the reaction was quenched. A yellow solid was obtained after filtration and concentration. This yellow solid was dissolved in 170 mL of HNO _{3 (aq)} (50%) and refluxed for 4 hours. The solution was then diluted to 1 L, filtered, and washed with water and acetone. After concentrating the solution, the product was obtained as a white solid (6.12 g, 93%) and identified using ¹ H NMR spectroscopy.

(2) 4,4'- Dimethoxycarbonyl -2,2'- Synthesis of bipyridine

The synthesis scheme of 4,4'-dimethoxycarbonyl-2,2'-bipyridine is provided as follows:

4,4'-Dicarboxy-2,2'-bipyridine (6.12 g) was dissolved in 115 mL of MeOH _(aq) and 15 mL of H ₂ SO _{4 (aq)} . The solution was refluxed at ~ 90–100 ° C for 24 hours, after which the reaction was quenched with 300 mL of DDW. NaOH _{(aq) was added} until the pH reached ~ 8.0. The organic layer was extracted with dichloromethane (2 × 50 mL) and dried over MgSO ₄ . It was then filtered and concentrated in a vacuum evaporator to give a solid product (5.9 g, 87%). Compounds were identified using ¹ H NMR spectroscopy.

(3) 4,4'- double ( Methylol ) -2,2'- Bipyridine Synthesis

The synthesis scheme of 4,4'-bis (hydroxymethyl) -2,2'-bipyridine is provided as follows:

4,4'-dimethoxycarbonyl-2,2'-bipyridine (5.9 g) was dissolved in pure EtOH, and sodium borohydride (12 g) was added thereto. The mixture was refluxed at ~ 90-100 ° C for 3 hours. After cooling to room temperature, saturated NH ₄ Cl (aq) was added, followed by 300 mL of DDW. The solution was then extracted with ethyl acetate (5 × 250 mL), dried over MgSO ₄ , filtered in a vacuum evaporator and concentrated to obtain the desired solid (4.46 g, 95%). The product was identified using ¹ H NMR spectroscopy.

(4) 4,4'- double ( Bromomethyl ) -2,2'- Synthesis of bipyridine

The synthesis scheme of 4,4'-bis (bromomethyl) -2,2'-bipyridine is provided as follows:

4,4'-bis (hydroxymethyl) -2,2'-bipyridine (4.46 g) was dissolved in 30 mL of HBr (48%) and 10 mL of concentrated sulfuric acid. The solution was then refluxed at 110 ° C for 6 hours. When the solution changed from pale yellow to gold, remove the heat source and add 100 mL of DDW to quench the reaction. The pH of the solution was adjusted to 7.0 with NaOH (aq), which caused the precipitation of pink compounds. The precipitate was collected via filtration, washed with DDW, and dried under vacuum. With ethyl acetate (2 × 50 mL) and extracted liquid fraction, dried MgSO _4, filtered, and concentrated in a vacuum evaporator. The desired product (4.39 g, 88%) was obtained and identified via ¹ H NMR spectroscopy.

(5) cation 2,2'- Synthesis of bipyridine ligand

The synthetic scheme of the cationic 2,2'-bipyridine ligand is provided as follows:

4,4'-bis (bromomethyl) -2,2'-bipyridine (0.5 g) was dissolved in dichloromethane and 20 mL of trimethylamine (50%) was added. The mixture was allowed to stand at room temperature for 24 hours to react. A freeze dryer was used for 2 days to remove all water and to obtain the desired product.

Preparation of water-soluble palladium catalyst

In a specific embodiment of the present invention, the palladium catalyst is PdCl ₂ (NH ₃ ) ₂ , which is also referred to as Pd (NH ₃ ) ₂ Cl ₂ . The water-soluble palladium catalyst can be prepared according to the following scheme:

This cationic 2,2'-bipyridyl ligand (0.2 mmol) was dissolved in 5 mL of water in a round bottom flask to form solution A. PdCl ₂ (NH ₃ ) ₂ (0.2 mmol) was dissolved in 10 mL of water in different round bottom flasks to form solution B. Solution A was slowly added to solution B under ultrasonic vibration to produce a cloudy solution, which eventually became clear. Finally, solution B was completely converted into solution A using 5 mL of water until the solution was completely clear. The obtained water-soluble palladium catalyst had a concentration of 0.2 mmol / 20 mL (ie, 0.01 mmol / mL). This solution was diluted to prepare an aqueous palladium catalyst solution, the concentration of which was 0.001 and 0.0001 mmol / mL.

Suzuki interactive coupling reaction

The Suzuki interactive coupling reaction scheme is provided as follows (Wu et al., Tetrahedron Letters. 47: 9267-9270, 2006):

The starting material (1 mmol), arylboronic acid (1.5 mmol), K ₂ CO ₃ (2 mmol), and H ₂ O (2 mL) were packed in a sealable tube equipped with a magnetic stir bar. In the case of styrene, TBAB (1 mmol) must be added. After adding Pd (NH ₃ ) ₂ Cl ₂ / L aqueous solution, the tube was sealed in air using a Teflon-coated screw cap. The reaction vessel was then placed in an oil bath at 100 ° C or no higher for 24 hours. After the reaction mixture was cooled to room temperature, the aqueous solution extracted with ethyl acetate, the organic phase was dried over MgSO _4, and the solvent was removed in vacuo. Silica-on-column chromatography provides the desired product.

In one embodiment of the present invention, the Suzuki cross-coupling reaction is performed at a temperature not higher than 100 ° C.

Recovery of water-soluble palladium catalyst

A scheme for recovering water-soluble palladium catalyst is provided as follows (Wu et al., Tetrahedron Letters. 47: 9267-9270, 2006):

Fill a sealable tube equipped with a magnetic stir bar with starting material (1 mmol), 4-chlorophenylboronic acid (1.5 mmol), K ₂ CO ₃ (2 mmol), and H ₂ O (2 mL) . In the case of styrene, TBAB (1 mmol) must be added. After adding Pd (NH ₃ ) ₂ Cl ₂ / L aqueous solution, the tube was sealed in air using a Teflon-coated screw cap. The reaction vessel was then placed in an oil bath at 100 ° C for 24 hours. After the reaction mixture was cooled to room temperature, the aqueous solution extracted with ethyl acetate, the organic phase was dried over MgSO _4, and the solvent was removed in vacuo. The desired product was obtained using silica column chromatography. After the reaction, the aqueous reaction mixture was washed three times with ethyl acetate with vigorous stirring, and the organic product was separated from the combined organic phase according to the procedure previously described. Next, 4-chlorophenylboronic acid and K ₂ CO ₃ were charged in the residual aqueous solution for the next reaction. In the case of styrene, TBAB needs to be added for the first operation.

Protection group

Any protecting group commonly used in the technology can be used in the present invention. For example, fluorenyl protecting groups are commonly used in carbohydrate chemistry, and alkyl ethers are used for ether protection to identify and analyze polysaccharides, cyclic acetals, or cyclic ketals in acetal protection, and protecting groups such as : N -ethenyl and phthalate) and other protecting groups. Some commonly used protecting groups are listed below: (1) Ester: Ac; Bz; Piz; (2) Ether: Benzyl (Bn); p MBn; All; (3) acetal (ketal): Tr; TES; TBDMS; (4) Amine: N- Ac; AcCl; THP.

According to the present invention, a new xylose derivative having the general formula I Formula I, wherein m in (R) m is an integer from 1 to 4; R is CH ₃ , OCH ₃ , or a halogen atom. In an example of the present invention, the xylose derivative is one selected from the group consisting of: 2- (4'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 1); 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2); 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3); 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4); 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5); 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6); 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7); 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8); 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9); and 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piran-3,4,5-triol (Compound 10).

The following examples further illustrate the present invention, which is intended to be exemplary rather than limiting.

Examples

Example 1 Preparation of starting materials

Regarding the synthesis of xylose derivatives, 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol is used as a starting material as follows:

The overall reaction scheme of the starting materials is provided as follows:

The crude product was purified by silica gel column chromatography and the product was obtained as a white powder with a yield of 45.9%. Figure 1A shows the ¹ H NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by the peaks of hydrogen atoms in the tetrahydrofuran and hydroxyl groups In the range of δ ~ 3.00–5.50 ppm. FIG. 1B shows the ¹³ C NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, in which the solvent peak appears at δ 43.5 ppm and at xylose The hydroxyl group at the C1 position appears at δ 2.0 ppm. However, the peak at δ 2.0 ppm disappeared in Figure 1A, rather than the peak corresponding to the benzene ring. Therefore, it was confirmed that the expected product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.59 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H). ¹³ C NMR (50 MHz, CD ₆ SO): δ 160.37, 141.89, 122.97, 104.79, 86.72, 80.27, 76.93, 73.24, 69.62. Mass calculated for C ₁₁ H ₁₃ IO ₄ : 336.08.

Preparation Examples of Synthetic Xylose Derivatives

The starting material obtained in Example 1 was used to synthesize a xylose derivative via a Suzuki interactive coupling reaction with a palladium catalyst in an aqueous solution. Ar-B (OH) ₂

10 kinds of xylose derivatives were synthesized. The following examples provide their purification and characteristics. The catalytic results of xylose and arylboronic acid (Ar-B (OH) ₂ ) are provided in Table 1. Table 1: Catalytic results of xylose and arylboronic acid.

Example 2

2- (4'-Chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 1):

The crude product was purified by silica gel column chromatography to yield a purified product as a white powder with a yield of 79.2%. 2A and 2B show ¹ H NMR spectra of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIGS. 2C and 2D show 2- (4'-chloro-biphenyl-4-yloxy) tetrahydro -2 H - pyran-3,4,5-triol The ¹³ C NMR spectra. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the hydrogen peak shifted from δ7.71 to 7.59 ppm. As shown in Figures 2A-2D, it was confirmed that the desired product was obtained.

¹ H NMR (200 MHz, CD ₆ SO): δ 7.64 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8 Hz, 2H), 7.46 (d, J = 8.6, 2H), 7.08 ( d, J = 8.8 Hz, 2H). ¹³ C NMR (50 MHz, CD ₆ SO): δ156.89, 138.4, 132.39, 131.55, 128.86, 127.86, 127.52, 116.73, 100.86, 76.3, 72.97, 69.26, 65.61. Mass calculated for C ₁₇ H ₁₈ O ₅ : 302.12.

Example 3

2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2):

The crude product was purified by silica gel column chromatography and the product was obtained as a white powder with a yield of 54.5%. 3A and 3B show ¹ H NMR spectra of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 3C shows a ¹³ C NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, ie 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, this hydrogen resonance was transferred from δ7.71 to 7.55 ppm. As shown in Figures 3A-3C, it was confirmed that the desired product was obtained.

¹ H NMR (200 MHz, CD ₆ SO): δ 7.55 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.8Hz, 2H), 2.32 (s, 3H). ¹³ C NMR (50 MHz, CD ₆ SO): δ156.45, 136.77, 135.96, 133.79, 129.25, 127.25, 125.99, 116.70, 101.01, 76.37, 69.30, 65.63, 20.53. Mass calculated for C ₁₈ H ₂₀ O ₅ : 316.13.

Example 4

2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 78.6%. Figures 4A and 4B show the ¹ H NMR and ¹³ C NMR spectra of 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, respectively. . In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the chemical transfer of this hydrogen atom was transferred from δ7.71 to 7.54 ppm. As shown in Figures 4A and 4B, it was confirmed that the desired product was obtained.

¹ H NMR (200 MHz, CD ₆ SO): δ 7.54 (d, J = 4.0 Hz, 2H), 7.47 (d, J = 8 Hz, 2H), 3.69 (s, 3H). ¹³ C NMR (50 MHz, CD ₆ SO): δ158.59, 156.16, 133.64, 127.25, 127.03, 116.72, 114.23, 101.04, 76.39, 73.03, 69.33, 65.64, 55.10. Mass calculated for C ₁₈ H ₂₀ O ₆ : 316.13.

Example 5

2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4):

The crude product was purified by silica gel column chromatography to obtain a white powder product with a yield of 51.8%. 5A and 5B show ¹ H NMR spectra of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 5C shows a ¹³ C NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.25 ppm. As shown in Figures 5A-5C, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.25 (d, J = 7.28 Hz, 3H), 7.23 (t, J = 7.4 Hz, 2H), 7.16 (d, J = 4.48 Hz, 2H), 7.06 (d, J = 4.48 Hz. 2H), 2.22 (s, 3H). ¹³ C NMR (100 MHz, CD ₆ SO): δ156.66, 141.34, 135.36, 135.22, 130.76, 130.44, 130.01, 127.52, 126.38, 116.46, 101.45, 76.95, 73.58, 69.87, 66.20, 20.71. Mass calculated for C ₁₈ H ₂₀ O ₅ : 316.13.

Example 6

2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 59.3%. 6A and 6B, which are provided 2- (2'-chloro-biphenyl-4-yloxy) tetrahydro - 2H - pyran-3,4,5-triol The ¹ H NMR and ¹³ C NMR spectrum. These peaks in the range of δ ~ 3.00-5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.39 ppm. As shown in Figures 6A and 6B, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.53 (d, 6.8 Hz, 1H), 7.39 (d, J = 4.8 Hz, 2H), 7.37 (d, J = 4.4 Hz, 1H), 7.35 ( t, 6.8Hz, 2H), 7.08 (d, J = 8.8 MHz, 2H). ¹³ C NMR (100 MHz, CD ₆ SO): δ156.24, 138.87, 131.78, 130.94, 130.85, 129.81, 129.27, 128.34, 126.94, 115.44, 100.37, 75.92, 72.55, 68.85, 65.20. Mass calculated for C ₁₇ H ₁₇ ClO ₅ : 336.13.

Example 7

2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 60.8%. 7A and 7B show ¹ H NMR spectra of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 7C shows a ¹³ C NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.39 ppm. As shown in Figures 7A-7C, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.39 (d, 6.84 Hz, 2H), 7.32 (t, 5.24 Hz, 1H), 7.25 (d, 7.32 Hz, 1H), 7.09 (d, 6.16 Hz 1H), 7.04 (d, 7.04 Hz, 1H), 7.00 (d, 5.96 Hz, 2H). ¹³ C NMR (100 MHz, CD ₆ SO): δ159.19, 156.34, 140.70, 133.25, 129.35, 127.22, 118.10, 116.18, 111.92, 111.32, 100.46, 75.90, 72.54, 68.83, 65.16, 54.54. Mass calculated for C ₁₈ H ₂₀ O ₆ : 332.13.

Example 8

2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 87.5%. 8A and 8B show ¹ H NMR spectra of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 8C shows a ¹³ C NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen shifted from δ7.71 to 7.57 ppm . As shown in Figures 8A-8C, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.57 (d, 11.6 Hz, 2H), 7.41 (s, 1H), 7.30 (t, 6.4 Hz, 1H), 7.12 (d, 8H, 1H), 7.05 (d, 2.8 Hz, 2H), 2.49 (s, 3H). ¹³ C NMR (100 MHz, CD ₆ SO): δ159.19, 139.16, 137.39, 133.51, 128.19, 127.8, 126.41, 122.87, 116.20, 100.49, 75.90, 72.55, 68.84, 65.17, 20.56. Mass calculated for C ₁₈ H ₂₀ O ₅ : 316.12.

Example 9

2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 92.0%. 9A and 9B show ¹ H NMR spectra of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol. FIG. 9C shows a ¹³ C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.59 ppm. As shown in Figures 9A-9C, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.59 (d, J = 3.6 Hz, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 7.12 (s, 1H), 7.07 (D, J = 8.8Hz, 2H), 6.88 (d, J = 8.4, 1H), 3.75 (s, 3H). ¹³ C NMR (100 MHz, CD ₆ SO): δ159.18, 156.34, 140.70, 133.25, 129.34, 127.21, 118.09, 116.18, 111.91, 111.30, 100.46, 75.89, 72.53, 68.83, 65.16, 54.54. Mass calculated for C ₁₈ H ₂₀ O ₆ : 332.13.

Example 10

2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 77.2%. 10A and 10B show ¹ H NMR spectra of 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. FIG. 10C shows a ¹³ C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, namely 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.63 ppm. As shown in Figures 10A-10C, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.66 (s, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 9.8 Hz, 1H), 7.45 (t, J = 8.0 Hz 1H), 7.35 (d, J = 2 Hz, 1H), 7.10 (d, J = 11.6 Hz, 2H). ¹³ C NMR (100 MHz, CD ₆ SO): δ156.23, 138.86, 131.77, 130.93, 130.84, 129.80, 129.26, 128.31, 126.92, 115.43, 110.36, 75.91, 72.54, 68.86, 65.19. Mass calculated for C ₁₇ H ₁₇ ClO ₅ : 336.08.

Example 11

2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 10):

The crude product was purified by silica gel column chromatography to obtain the product as a white powder with a yield of 98.0%. 11A and 11B show the ¹ H NMR of 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piran-3,4,5-triol and ¹³ C NMR spectrum. In this spectrum, the peaks in the range of δ to 3.00 to 5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion. Due to the presence of iodine in the starting material, that is, 2- (4-iodophenoxy) tetrahydro- 2H -piperan-3,4,5-triol, the resonance of this hydrogen atom was transferred from δ7.71 to 7.07 ppm. As shown in FIGS. 11A and 11B, it was confirmed that the desired product was obtained.

¹ H NMR (400 MHz, CD ₆ SO): δ 7.56 (d, J = 8.8 Hz, 2H), 7.21 (s, 2H), 7.07 (d, J = 8.8 Hz, 2H), 6.95 (s, 1H ), 2.32 (s, 6H). ¹³ C NMR (100 MHz, CD ₆ SO): δ156.12, 139.14, 137.21, 133.62, 127.74, 127.60, 123.60, 116.14, 110.49, 75.89, 72.54, 68.83, 65.17, 20.47. Mass calculated for C ₁₉ H ₂₂ O ₅ : 330.15.

no

The foregoing summary of the invention and the following embodiments of the present invention will be better understood when read in conjunction with the accompanying drawings.

In these schemes:

Figure 1A shows the ¹ H NMR spectrum of the starting material 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by hydrogen atoms of the tetrahydrofuran and the hydroxyl moiety The peak in the range of δ ~ 3.00–5.50 ppm, where the peak at 2.0 ppm disappears, instead of corresponding to the peak of the benzene ring.

Figure 1B shows the ¹³ C NMR spectrum of 2- (4-iodophenoxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by a solvent peak at ∂ 43.5 ppm and at xylose The hydroxyl group at the C1 position appears at δ 2.0 ppm.

FIG. 2A shows a ¹ H NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ to 3.00. Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 2B shows an enlarged view of a ¹ H NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 2C shows a ¹³ C NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 2D shows an enlarged ¹³ C NMR spectrum of 2- (4′-chlorobiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 3A shows a ¹ H NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ to 3.00 The peaks in the –5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions.

FIG. 3B shows an enlarged view of a ¹ H NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 3C shows a ¹³ C NMR spectrum of 2- (4′-methylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 4A shows a ¹ H NMR spectrum of 2- (4′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00 Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 4B shows a ¹³ C NMR spectrum of 2- (4′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 5A shows a ¹ H NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol. The peak in the range of δ to 3.00-5.50 ppm corresponds to the hydrogen atom of the hydroxyl group and the tetrahydrofuran portion.

FIG. 5B shows an enlarged view of a ¹ H NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 5C shows a ¹³ C NMR spectrum of 2- (2′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 6A shows the ¹ H NMR spectrum of 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ ~ 3.00– The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 6B shows a ¹³ C NMR spectrum of 2- (2′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 7A shows the ¹ H NMR spectrum of 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by δ ~ Peaks in the range of 3.00–5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran portions.

FIG. 7B shows an enlarged view of the ¹ H NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 7C shows a ¹³ C NMR spectrum of 2- (2′-methoxybiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

FIG. 8A shows a ¹ H NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ ~ 3.00– The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 8B shows an enlarged view of the ¹ H NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 8C shows a ¹³ C NMR spectrum of 2- (3′-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 9A shows the ¹ H NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00 Peaks in the range of –5.50 ppm correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 9B shows an enlarged view of the ¹ H NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 9C shows a ¹³ C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 10A shows a ¹ H NMR spectrum of 2- (3′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol, which is characterized by δ to 3.00- The peaks in the 5.50 ppm range correspond to the hydrogen atoms of the hydroxyl and tetrahydrofuran moieties.

FIG. 10B shows an enlarged view of the ¹ H NMR spectrum of 2- (3′-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 10C shows a ¹³ C NMR spectrum of 2- (3′-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol.

FIG. 11A shows a ¹ H NMR spectrum of 2- (3 ′, 5′-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol, which is characterized by: The peaks in the range of δ to 3.00–5.50 ppm correspond to the hydrogen atoms of the hydroxyl group and the tetrahydrofuran portion.

FIG. 11B shows a ¹³ C NMR spectrum of 2- (3 ′, 5′-dimethylbiphenyl-4-yloxy) tetrahydro-2 H -piperan-3,4,5-triol.

no

Claims (9)

A xylose derivative having the general formula I: Formula I, wherein m in (R) m is an integer from 1 to 4; R is CH ₃ , OCH ₃ , or a halogen atom. The xylose derivative of claim 1, which is selected from one of the group consisting of: 2- (4'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 1); 2- (4'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 2); 2- (4'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 3); 2- (2'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 4); 2- (2'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 5); 2- (2'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 6); 2- (3'-methylbiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 7); 2- (3'-methoxybiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (compound 8); 2- (3'-chlorobiphenyl-4-yloxy) tetrahydro- 2H -piperan-3,4,5-triol (Compound 9); and 2- (3 ', 5'-dimethylbiphenyl-4-yloxy) tetrahydro- 2H -piran-3,4,5-triol (Compound 10). A method for synthesizing a xylose derivative as claimed in claim 1, comprising the steps of: protecting xylose with a protecting group, and then incorporating a halogen atom as a leaving group; removing the protecting group and using a water-soluble complex The Suzuki cross-coupling reaction with a palladium catalyst in an aqueous solution was performed to synthesize the xylose derivative. The method of claim 3, wherein the halogen atom is an iodine atom. The method of claim 3, wherein the water-soluble ligand is recovered. The method of claim 3, wherein the palladium catalyst is recovered. The method of claim 3, wherein the palladium catalyst is PdCl ₂ (NH ₃ ) ₂ and the water-soluble ligand is a cationic 2,2′-bipyridine ligand. The method of claim 7, wherein the cationic 2,2'-bipyridine ligand is dissolved in water to form solution A; and PdCl ₂ (NH ₃ ) _{2 is} dissolved in water to form solution B; and the solution A is added to Solution B to produce a cloudy solution, which eventually became clear to obtain a water-soluble palladium catalyst. The method of claim 3, wherein the Suzuki cross-coupling reaction is performed at a temperature higher than 100 ° C.