Benzofuran monomer compounds from Choerospondias axillaris and their application

Abstract

The present invention provides a benzofuran monomer compound in Choerospondias axillaris and its application in preparing food and medicine. It belongs to the field of pharmaceutical technology. The present invention obtains 2-[10'(Z)-pentadecenyl]-benzofuran-5-ol, i.e., 2-[10'(Z)-pentadecenyl]-benzofuran-5-ol and 2-[8'(Z)-tridecenyl]-benzofuran-5-ol, i.e., 2-[8'(Z)-tridecenyl]-benzofuran-5-ol, from the fresh fruit of Choerospondias axillaris. The thin layer chromatography method is mainly used for guidance and combined with other phytochemical research methods. An α-glucosidase inhibitory activity evaluation model is used, and a solid, liquid or paste dosage form is prepared according to a conventional method to achieve the therapeutic effect of lowering blood sugar. The preparation method of the benzofuran monomer compound described in the present invention is simple, high in yield, and excellent in purity, and the obtained compound is a natural secondary metabolite with significant α-glucosidase inhibitory activity.

Description

Technical field:

[0001] The present invention belongs to the field of medical technology, and specifically relates to a benzofuran monomer compound in Choerospondias axillaris and a pharmaceutical composition thereof, as well as a preparation method and application thereof, and an application thereof in the preparation of an alpha-glucosidase inhibitor and an application thereof in the preparation of a drug for preventing or treating diabetes. Background technology:

[0002] Diabetes is one of the three most serious diseases affecting human health, posing a serious threat to the life and quality of life of patients. According to incomplete statistics, there are about 520 million diabetic patients in the world, of which more than 90% are diabetic patients. Diabetes mellitus ...

[0003] α-Glucosidase and oligosaccharide hydrolase are located in the brush border of small intestinal epithelial cells. They are key enzymes that catalyze the cleavage of α-1,4 bonds in α-glucose and α-oligosaccharides to release glucose and increase postprandial blood glucose levels. The enhancement of the enzyme activity leads to increased postprandial blood glucose levels, inducing obesity and diabetes. Inhibiting the activity of α-glucosidase is an effective way to treat type II diabetes. At present, acarbose tablets and miglitol tablets commonly used to treat type II diabetes have certain side effects. Plant-derived natural blood sugar-lowering substances have fewer toxic and negative effects, longer-lasting efficacy, and are more acceptable to patients than synthetic drugs.

[0004] Choerospondias australis, also known as five-eyed fruit and snot fruit, is a plant of the genus Choerospondias in the Anacardiaceae family. It is mainly distributed in Jiangxi, Yunnan, Guangxi, Hunan, Guizhou, Sichuan and other places in my country, and is also distributed in India, Japan, Indochina and other countries and regions. Choerospondias australis fresh fruit tastes sour and astringent, and the flesh is rich in nutrients such as amino acids, dietary fiber, minerals, sugars, etc., and is often used to make fruit treasures, beverages, preserved fruits and condiments. In addition, the fruit is also rich in chemical components such as flavonoids and polyphenols, which have the effects of promoting qi and blood circulation, nourishing the heart and calming the mind, and removing accumulation and detoxification. Recent studies have reported that a series of flavantriols, flavonoids, amino acids and terpenoid components have been isolated from Choerospondias australis. However, to date, the prior art has no benzofuran monomer compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol derived from the plant, and there is no report on the compound and its composition as a hypoglycemic drug. Summary of the invention:

[0005] The purpose of the present invention is to provide compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, their preparation methods, pharmaceutical compositions containing them, and their use in the preparation of hypoglycemic drugs.

[0006] In order to achieve the above-mentioned object of the present invention, the present invention provides the following technical solutions:

[0007] Compound 1 shown in the following structural formula: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol,

[0008]

[0009] The preparation method of the compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and the compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol comprises the following steps: crushing the fresh fruit of Choerospondias australis, using 1.5 times the volume of 80% acetone aqueous solution to cold-immerse and extract at room temperature for 4 times, each time for 7 days, filtering, concentrating the filtrate under reduced pressure at 50°C to remove the organic solvent to obtain a crude sample extract, suspending the crude extract with water, extracting with ethyl acetate, wherein the ethyl acetate layer is partially concentrated under reduced pressure to remove the organic solvent, and then applied to a Sephadex LH-20 chromatography column, and in MeOH:H 2 O volume ratio of 0:1 to 1:0 gradient elution to obtain Fr.1 to Fr.6, wherein Fr.6 was subjected to silica gel column chromatography, MeOH:CHCl 3The volume ratio was 0:1-1:0 and the gradient elution was used to obtain Fr.6-1 to Fr.6-5; Fr.6-4 was subjected to RP-18 column chromatography, MeOH:H 2 O volume ratio of 0:1 ~ 1:0 gradient elution to obtain Fr.6-4-1 to Fr.6-4-4, wherein Fr.6-4-4 was prepared on aQ column, CH 3 CN:H 2 O volume ratio of 82:18 to obtain compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, and the purity was ≥90% after HPLC content detection.

[0010] The compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or the compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol are used in the preparation of α-glucosidase inhibitors.

[0011] Use of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol in the preparation of drugs for preventing or treating diabetes.

[0012] A pharmaceutical composition comprising the compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or the compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, and a pharmaceutically acceptable carrier.

[0013] The preparation method of the pharmaceutical composition is to obtain compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol according to the above-mentioned method for preparing the compound, and then add a pharmaceutically acceptable carrier.

[0014] The application of the pharmaceutical composition in preparing medicine for preventing or treating diabetes.

[0015] The present invention provides compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, which are derived from the fruits and other parts of Ziziphus axillaris and plants of the same genus, and secondary metabolites of other plants and fungi containing the compounds.

[0016] The compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and the compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol provided by the present invention have significant α-glucosidase inhibitory activity.

[0017] When the compound is used to prepare a drug, the present invention preferably uses the compound directly or in the form of a pharmaceutical composition.

[0018] The pharmaceutical composition provided by the present invention comprises the above-mentioned compound and a pharmaceutically acceptable carrier. In the present invention, the pharmaceutically acceptable carrier is preferably a solid, semi-solid or liquid diluent, a filler and a pharmaceutical product adjuvant. The present invention has no particular limitation on the pharmaceutically acceptable carrier, and any pharmaceutically acceptable carrier well known in the art, non-toxic and inert to humans and animals can be selected.

[0019] The present invention has no particular limitation on the method for preparing the pharmaceutical composition. The compound can be directly mixed with a pharmaceutically acceptable carrier. The present invention has no particular limitation on the mixing process. The pharmaceutical composition can be obtained by selecting a process well known in the art.

[0020] The present invention provides the use of the pharmaceutical composition described in the above technical solution in the preparation of hypoglycemic drugs. There is no special limitation on the method of the application, and any method well known in the art can be used.

[0021] In the present invention, when the pharmaceutical composition is used to prepare a drug, the content of the composition in the drug is preferably 0.1-99%; in the pharmaceutical composition, the content of the compound in the pharmaceutical composition is preferably 0.5-90%. The pharmaceutical composition of the present invention is preferably used in the form of a dosage per unit body weight. In the present invention, the prepared drug can preferably be administered in two forms: injection (intravenous injection, intramuscular injection) and oral administration.

[0022] The present invention provides a method for evaluating the hypoglycemic activity of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol. The α-glucosidase inhibition activity model is used for evaluation. Step 1, prepare 0.1 mol / L phosphate buffer (pH 6.8), and dissolve the sample to be tested in DMSO. Step 2, the reaction mixture (200 μL) includes the sample to be tested (final concentration 1-50 μM), phosphate buffer (pH 6.8, 0.1 M), 4-nitrophenylα-D-glucopyranoside (PNPG, 1 mM), and α-glucosidase enzyme solution (final concentration 0.025 U / mL) are sequentially added to a 96-well ELISA plate, fully mixed, and 3 wells are set to repeat. At the same time, DMSO solvent was set as a blank control and quercetin (final concentration 2-10 μM) / acarbose (final concentration 50-300 μM) was set as a positive control. Step 3, after the reaction solution was incubated at 37°C for 50 minutes, the absorbance value A at 405 nm was measured using an ELISA reader. Step 4, the inhibition rate of α-glucosidase inhibitory activity was calculated according to the following formula: Inhibition rate (%) = (A blank control -A sample ) / A blank control ×100;IC 50 The value is calculated according to the Reed & Muench method.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] 1. The present invention provides two new compounds 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol.

[0025] 2. The present invention provides a new method for preparing a new compound, which has readily available raw materials, is easy to operate, and is suitable for industrial production.

[0026] 3. The present invention provides a pharmaceutical composition with a new compound as an active ingredient, providing a new drug with better medicinal effects for new hypoglycemic drugs.

[0027] 4. Evaluation of the hypoglycemic activity of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol of the present invention: The evaluation was carried out according to the α-glucosidase inhibitory activity evaluation method described in the content of the invention. The results showed that the α-glucosidase inhibitory activity IC of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol was50 The value was 3.53±0.12μM, which was significantly stronger than the positive control quercetin (IC 50 =5.22±0.25μM) and acarbose (IC 50 =229.0±0.4 μM). Compound 2: α-glucosidase inhibitory activity IC of 2-[8′(Z)-tridecenyl]-benzofuran-5-ol 50 The value was 2.26±0.06μM, which was significantly stronger than the positive control quercetin (IC 50 =5.22±0.25μM) and acarbose (IC 50 =229.0±0.4μM). Description of the drawings:

[0028] Figure 1 Schematic diagrams of the structural formulas of benzofuran monomer 1 (Compound 1): 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and Compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol of the present invention. Specific implementation method:

[0029] In order to better understand the essence of the present invention, the following embodiments of the present invention are used in conjunction with the accompanying drawings to further illustrate the benzofuran monomer 1 (Compound 1): 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, and their preparation methods, structural identifications, and pharmacological effects, but the present invention is not limited to these test examples and embodiments.

[0030] In conjunction with the embodiments of the present invention, the technical solutions of the present invention are clearly and completely described. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] Example 1

[0032] Preparation of compound 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol (Compound 1) and evaluation of its hypoglycemic activity.

[0033] Preparation of compound 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol: fresh jujube fruit (95 kg) was crushed, and 80% acetone aqueous solution (143 L) was cold-extracted at room temperature for 4 times, each time for 7 days, filtered, and the filtrate was concentrated under reduced pressure at 50°C to remove the organic solvent to obtain a crude sample extract, which was suspended in water and extracted with ethyl acetate. The ethyl acetate layer was partially concentrated under reduced pressure to remove the organic solvent to obtain 732 g of extract, 300 g of which was applied to a Sephadex LH-20 chromatography column and precipitated in MeOH:H 2 O volume ratio of 0:1 ~ 1:0 gradient elution to obtain Fr.1 to Fr.6, of which Fr.6 (43g) was subjected to silica gel column chromatography, MeOH: CHCl 3 Fr.6-1 to Fr.6-5 were obtained by gradient elution with a volume ratio of 0:1-1:0; Fr.6-4 (5 g) was subjected to RP-18 column chromatography with MeOH:H 2 O volume ratio of 0:1 ~ 1:0 gradient elution to obtain Fr.6-4-1 to Fr.6-4-4, wherein Fr.6-4-4 was prepared on aQ column, CH 3 CN:H 2 O volume ratio of 82:18, at t r =50.5min, compound 1 (6 mg) was obtained, and its purity was ≥90% as determined by HPLC.

[0034] Structural identification of compound 1: Compound 1 is a colorless amorphous powder. According to HRESIMS data (m / z 341.2479 [MH] - , calculated value is 341.2486), the molecular formula of compound 1 is inferred to be C 23 H 34 O 2 The specific rotation value is 1 The H spectrum (Table 1) shows four aromatic proton signals [δ H 7.15 (1H, d, J = 8.7 Hz), 6.84 (1H, d, J = 2.5 Hz), 6.66 (1H, dd, J = 8.7, 2.5 Hz), 6.25 (1H, s)]. The HMBC spectrum showed that from H-7 (δ H 7.15) to C-5(δ C 153.9) and C-3′(δ C 131.1), from H-6 (δ H 6.66) to C-4 (δ C 106.1) and C-7′(δ C 150.6), from H-4 (δ H 6.84) to C-7′ and C-6 (δ C112.5), from H-3 (δ H 6.25) to C-4 and C-7′, from H-1″ (δ H 2.67) to C-3(δ C 102.8) and C-4, from H-2″(δ H 1.68) to C-2(δ C 161.4) is related. In addition, the aromatic protons H-6 / H-7, H-1″ / H-2″ 1 H- 1 H COSY correlation indicates that the compound structure contains benzofuran aromatic fragments. In addition, the methylene proton signal [δ H 2.67 (2H, t, J = 7.6 Hz), 2.00 (4H, m), 1.68 (2H, p, J = 7.4 Hz)], olefin proton signal [δ H 5.32 (2H, m)], terminal methyl proton signal [δ H 0.89 (3H, t, J = 7.0 Hz)], and a series of overlapping proton signals with chemical shifts between 1.24 and 1.35 (16H, m) indicated the presence of a long olefin chain in the structure of compound 1. 1 H spectrum and 13 The C spectrum signal is very similar to the data of the known compound choerosponol A (Kil et al., Journal of natural products, 2020, 83(3), 584-592), but the carbon signals corresponding to two methylene groups are missing in the unsaturated hydrocarbon chain of compound 1. Therefore, the structure of compound 1 was determined to be 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol.

[0035] Table 1 Compound 1 13 C(150MHz) and 1 H (600 MHz) NMR spectrum data (CD 3 OD,δin ppm,J in Hz)

[0036]

[0037] Note: a Overlapping signals; chemical shifts determined by HSQC and HMBC correlation

[0038] Compound 1: 2-[10′(Z)-pentadecenyl]-benzaforan-5-ol hypoglycemic activity evaluation method, using α-glucosidase inhibition activity model for evaluation. Step 1, prepare 0.1 mol / L phosphate buffer (pH 6.8), and dissolve the sample to be tested in DMSO. Step 2, the reaction mixture (200 μL) including the sample to be tested (final concentration 1-50 μM), phosphate buffer (pH 6.8, 0.1 M), 4-nitrophenylα-D-glucopyranoside (PNPG, 1 mM), α-glucosidase enzyme solution (final concentration 0.025 U / mL) is sequentially added to a 96-well ELISA plate, mixed thoroughly, and set 3 wells for replication. At the same time, DMSO solvent is set as a blank control, quercetin (final concentration 2-10 μM) and acarbose (final concentration 50-300 μM) are set as positive controls. Step 3, after the reaction solution is incubated at 37°C for 50 min, the absorbance value A at 405 nm is measured using an enzyme marker. Step 4, the inhibition rate of α-glucosidase inhibitory activity is calculated according to the following formula: Inhibition rate (%) = (A blank control -A sample ) / A blank control ×100;IC 50 The value is calculated according to the Reed & Muench method.

[0039] The results showed that compound 1: 2-[10′(Z)-pentadecenyl]-benzaprofuran-5-ol has an α-glucosidase inhibitory activity IC 50 The value was 3.53±0.12μM, which was significantly stronger than the positive control quercetin (IC 50 =5.22±0.25μM) and acarbose (IC 50 =229.0±0.4μM).

[0040] Example 2

[0041] Preparation of compound 2-[8′(Z)-tridecenyl]-benzofuran-5-ol (Compound 2) and evaluation of its hypoglycemic activity.

[0042] Preparation of compound 2-[8′(Z)-tridecenyl]-benzofuran-5-ol: fresh jujube fruit (95 kg) was crushed, and 80% acetone aqueous solution (143 L) was cold-extracted at room temperature for 4 times, each time for 7 days, filtered, and the filtrate was concentrated under reduced pressure at 50°C to remove the organic solvent to obtain a crude sample extract, which was suspended in water and extracted with ethyl acetate. The ethyl acetate layer was partially concentrated under reduced pressure to remove the organic solvent to obtain 732 g of extract, 300 g of which was applied to a Sephadex LH-20 chromatography column and precipitated in MeOH:H 2O volume ratio of 0:1 ~ 1:0 gradient elution to obtain Fr.1 to Fr.6, of which Fr.6 (43g) was subjected to silica gel column chromatography, MeOH: CHCl 3 Fr.6-1 to Fr.6-5 were obtained by gradient elution with a volume ratio of 0:1-1:0; Fr.6-4 (5 g) was subjected to RP-18 column chromatography with MeOH:H 2 O volume ratio of 0:1 ~ 1:0 gradient elution to obtain Fr.6-4-1 to Fr.6-4-4, wherein Fr.6-4-4 was prepared on aQ column, CH 3 CN:H 2 O volume ratio of 82:18, at t r =35.3min, compound 2 (5 mg) was obtained, and its purity was ≥90% as determined by HPLC.

[0043] Structural identification of compound 2: Compound 2 is a colorless oil. According to HRESIMS data (m / z 337.2137 [M+Na] + , calculated value is 337.2138), the molecular formula of compound 2 is inferred to be C 21 H 30 O 2 The specific rotation value is 13 The C spectrum (Table 2) shows 21 carbon signals, which are attributed to 1 methyl, 10 methylene, 6 methine (2 olefins, 4 aromatics) and 4 quaternary carbons (1 carbonyl). 1 Four aromatic proton signals [δ H 7.16 (1H, d, J = 8.7 Hz), 6.83 (1H, d, J = 2.5 Hz), 6.65 (1H, dd, J = 8.7, 2.5 Hz), 6.27 (1H, s)]. H 7.16) to C-5(δ C 153.9) and C-3′(δ C 131.1), from H-6 (δ H 6.65) to C-4 (δ C 106.1) and C-7′(150.6), from H-4(δ H 6.83) to C-7′(δ C 150.6) and C-6 (112.5), from H-3 (δ H 6.27) to C-4 and C-7′, from H-1″ (δ H 2.69) to C-3 (δ C 102.8) and C-4, from H-2″(δ H 1.70) to C-2(δC 161.5), proving that the structure contained a benzofuran aromatic fragment. The 1D and 2D NMR data of compound 2 were similar to those of 1, except that the alkenyl chain lacked two methylene groups. Therefore, compound 2 was identified as 2-[8′(Z)-tridecenyl]-benzofuran-5-ol.

[0044] Table 2 Compound 2 13 C(150MHz) and 1 H (600 MHz) NMR spectrum data (CD 3 OD,δin ppm,J in Hz).

[0045]

[0046] Note: a Overlapping signals; chemical shifts determined by HSQC and HMBC correlation

[0047] Compound 2: 2-[8′(Z)-tridecenyl]-benzaforan-5-ol hypoglycemic activity evaluation method, using α-glucosidase inhibition activity model for evaluation. Step 1, prepare 0.1 mol / L phosphate buffer (pH 6.8), and dissolve the sample to be tested in DMSO. Step 2, the reaction mixture (200 μL) including the sample to be tested (final concentration 1-50 μM), phosphate buffer (pH 6.8, 0.1 M), 4-nitrophenylα-D-glucopyranoside (PNPG, 1 mM), α-glucosidase enzyme solution (final concentration 0.025 U / mL) are sequentially added to a 96-well ELISA plate, mixed thoroughly, and set 3 wells for replication. At the same time, DMSO solvent is set as a blank control, quercetin (final concentration 2-10 μM) and acarbose (final concentration 50-300 μM) are set as positive controls. Step 3, after the reaction solution is incubated at 37°C for 50 min, the absorbance value A at 405 nm is measured using an enzyme marker. Step 4, the inhibition rate of α-glucosidase inhibitory activity is calculated according to the following formula: Inhibition rate (%) = (A blank control -A sample ) / A blank control ×100;IC 50 The value is calculated according to the Reed & Muench method.

[0048] The results showed that compound 2: 2-[8′(Z)-tridecenyl]-benzaprofuran-5-ol has an α-glucosidase inhibitory activity IC 50 The value was 2.26±0.06μM, which was significantly stronger than the positive control quercetin (IC 50=5.22±0.25μM) and acarbose (IC 50 =229.0±0.4μM).

[0049] Formulation Example 1:

[0050] Compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol are added with injection water as conventionally, finely filtered, and sterilized by filling to prepare injection solution.

[0051] Formulation Example 2:

[0052] Take compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, dissolve or suspend them in sterile water for injection, stir and mix, filter with a sterile suction funnel, filter aseptically, divide into 2 ampoules, freeze-dry at low temperature, and aseptically seal them to obtain injections.

[0053] Formulation Example 3:

[0054] Take compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, add them to the excipient in a weight ratio of 9:1 to prepare a powder.

[0055] Formulation Example 4:

[0056] Take compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, add them to the excipients at a weight ratio of 1:5-1:10, and granulate and tablet.

[0057] Formulation Example 5:

[0058] Compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol are prepared into oral liquid according to a conventional oral liquid preparation method.

[0059] Formulation Example 6:

[0060] Take compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, add excipients at a weight ratio of 5:1 to the excipients to prepare capsules, granules or granules.

[0061] Formulation Example 7:

[0062] Take compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, add excipients at a weight ratio of 3:1 to the excipients, and prepare capsules, granules or granules.

Claims

1. Compound 1 shown in the following structural formula: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, 2. A method for preparing compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol as claimed in claim 1, characterized in that: The method comprises the following steps: crushing fresh jujube fruit, using 1.5 times the volume of 80% acetone aqueous solution to cold-immerse and extract 4 times at room temperature, each time for 7 days, filtering, concentrating the filtrate under reduced pressure at 50°C to remove organic solvent to obtain a crude extract, suspending the crude extract with water, extracting with ethyl acetate, wherein the ethyl acetate layer is partially concentrated under reduced pressure to remove the organic solvent and then subjected to Sephadex LH-20 chromatography column, gradient elution with MeOH:H2O volume ratio of 0:1 to 1:0 to obtain Fr.1 to Fr.6, among which Fr.6 was subjected to silica gel column chromatography, and gradient elution with MeOH:CHCl3 volume ratio of 0:1-1:0 to obtain Fr.6-1 to Fr.6-5; among which Fr.6-4 was subjected to RP-18 column chromatography, and gradient elution with MeOH:H2O volume ratio of 0:1 to 1:0 to obtain Fr.6-4-1 to Fr.6-4-4, among which Fr.6-4-4 was subjected to semi-preparative liquid phase aQ column, and eluted with CH3CN:H2O volume ratio of 82:18 to obtain compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol.

3. Use of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol as claimed in claim 1 in the preparation of α-glucosidase inhibitors.

4. Use of compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol as described in claim 1 in the preparation of drugs for preventing or treating diabetes.

5. A pharmaceutical composition comprising the compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and / or the compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol as described in claim 1, and a pharmaceutically acceptable carrier.

6. Use of the pharmaceutical composition according to claim 5 in the preparation of a drug for preventing or treating diabetes.

7. The method for preparing the pharmaceutical composition according to claim 5, characterized in that: The method comprises the following steps: crushing fresh jujube fruit, using 1.5 times the volume of 80% acetone aqueous solution to cold-immerse and extract 4 times at room temperature, each time for 7 days, filtering, concentrating the filtrate under reduced pressure at 50°C to remove organic solvent to obtain a crude extract, suspending the crude extract with water, extracting with ethyl acetate, wherein the ethyl acetate layer is partially concentrated under reduced pressure to remove the organic solvent and then subjected to Sephadex LH-20 chromatography column, gradient elution with MeOH:H2O volume ratio of 0:1 to 1:0 to obtain Fr.1 to Fr.6, wherein Fr.6 is subjected to silica gel column chromatography, and gradient elution with MeOH:CHCl3 volume ratio of 0:1-1:0 to obtain Fr.6-1 to Fr.6-5; wherein Fr.6-4 is subjected to RP-18 column chromatography, and gradient elution with MeOH:H2O volume ratio of 0:1 to 1:0 to obtain Fr.6-4-1 to Fr.6-4-4, wherein Fr.6-4-4 is subjected to semi-preparative liquid phase aQ column, and eluted with CH3CN:H2O volume ratio of 82:18 to obtain compound 1: 2-[10′(Z)-pentadecenyl]-benzofuran-5-ol and compound 2: 2-[8′(Z)-tridecenyl]-benzofuran-5-ol, and then a pharmaceutically acceptable carrier is added.

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