Pseudo taraxasterol A ring and E ring derivative and application thereof

Abstract

The invention belongs to the technical field of medicine, and discloses a pseudo taraxasterol A ring and E ring derivative and application, the pseudo taraxasterol A ring derivative is a 3-site oxime derivative, and the pseudo taraxasterol E ring derivative is a 20-site and / or 21-site epoxy, ketone and oxime derivative. The pseudotaraxasterol and the derivative thereof prepared by the invention are simple in process and high in yield, the preparation of the derivative does not need conditions such as water-free and oxygen-free conditions, the reaction yield is high, and the used time is short. An activity test result shows that the derivative has relatively good alpha-glucosidase inhibitory activity. Therefore, the compound has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and relates to natural product derivatization and new applications, in particular to a derivative of the A-ring and E-ring of pseudotaraxasterol and its application. Background Art

[0002] With the improvement of living standards and the aggravation of social aging, the prevalence of diabetes has risen rapidly globally. Existing drugs still have certain limitations. For example, some patients do not respond well to existing drugs or cannot effectively control blood sugar; some drugs may cause side effects such as hypoglycemia and weight gain, affecting patient compliance. With the development of precision medicine, the demand for drugs for specific patient groups has increased. Therefore, the research and development of new anti-diabetic drugs has important market demand.

[0003] α-Glucosidase is one of the starch hydrolase enzymes, and it is also known as α-glucosidase hydrolase or glucosyltransferase (GTase). It hydrolyzes the α-glucosidic bond of the substrate from the non-reducing end of the polysaccharide to produce α-D-glucose, thereby increasing blood sugar in the human body. α-Glucosidase inhibitors delay the absorption of carbohydrates by inhibiting α-glucosidase on the brush border of the small intestinal mucosa, reducing postprandial hyperglycemia. The main characteristics are stable blood sugar lowering, high safety, and the ability to reduce the incidence of cardiovascular complications. It is one of the few oral hypoglycemic drugs that can intervene in impaired glucose tolerance. Common α-glucosidase inhibitors have various side effects, and it is of great significance to discover new α-glucosidases.

[0004] Pseudotaraxasterol, also known as psi-taraxasterolh or pseudotaraxasterol, is a naturally occurring pentacyclic triterpenoid compound of the ursane type, which is widely present in Compositae plants, such as Taraxacum, Aster, etc. In recent years, it has received extensive attention due to its various biological activities, such as anti-inflammatory, anti-Mycobacterium tuberculosis, anti-tumor, AChE inhibitory, anti-parasitic and other activities. Due to the low natural content and difficult purification of this compound, there are few reports on its structural derivatization and activity research.

[0005] Through retrieval, the following publicly available documents related to the present invention's patent application were found:

[0006] 1. Patent: Yang Hao, Li Xiang, etc. A derivative of pseudotaraxasterol, its preparation method and application, application number 2023111552565.5. This patent is the previous research of this research group, which discloses a series of derivatives of pseudotaraxasterol esterified at the 3-position hydroxyl group and their applications. However, the present invention synthesizes novel A-ring oxime derivatives and novel E-ring derivatives for the first time, and the structures are completely new.

[0007] 2. Journals and Magazines: Five centuries of Cirsium ehrenbergii Sch.Bip. (Asteraceae) in Mexico, from Huitzquilitl to Cardo Santo: History, ethnomedicine, pharmacology and chemistry [J]. Journal of Ethnopharmacology, 2023, 301: 115778. This article reported the isolation of compounds such as pseudotaraxasterol from the plant Cirsum ehrenbergii, but their structures are different from those of the present invention, and it did not mention that pseudotaraxasterol and its derivatives have hypoglycemic and α-glucosidase inhibitory activities.

[0008] By comparison, there are essential differences between the present invention and the above-mentioned published literature. Most of the literature reports the extraction and separation of natural pseudotaraxasterol. The previous research of this project only focused on the derivatization of the 3-hydroxy group at the A ring. However, the A-ring and E-ring derivatives synthesized in the present invention are all new compounds, and their structures and activities are discovered for the first time. Therefore, obtaining novel pseudotaraxasterol derivatives and their new applications is the motivation of the technical solution of the present invention. Summary of the Invention

[0009] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a pseudotaraxasterol A-ring and E-ring derivative and its application.

[0010] The technical solution adopted by the present invention to solve its technical problems is:

[0011] A pseudotaraxasterol A-ring and E-ring derivative, wherein the pseudotaraxasterol A-ring derivative is a 3-oxime derivative, and the pseudotaraxasterol E-ring derivative is a 20- and / or 21-epoxy, keto, and oxime derivative.

[0012] Furthermore, for the 3-oxime derivative of the pseudotaraxasterol A-ring, its general structural formula I is as follows:

[0013]

[0014] Among them, at the 3-position, R is oxime (=NOH), oxime carboxylate (=NOCOR’), where R’ is an alkyl group with 1-4 carbons, phenyl, substituted phenyl, benzyl, substituted benzyl, styrene, substituted styrene, a carboxylic acid with 2-4 carbons; or R is oxime ether (=NOR’), where R’ is an alkyl group with 1-4 carbons, phenyl, substituted phenyl, benzyl, substituted benzyl.

[0015] Furthermore, the preparation method of the 3-oxime derivative of the pseudotaraxasterol A-ring includes the following steps:

[0016] Using pseudo-taraxasterol (1) as the raw material, it is oxidized under conditions such as pyridinium chlorochromate (PCC) to obtain pseudo-taraxasterone (2). Then, through conditions such as hydroxylamine hydrochloride (NH2OH·HCl), the corresponding oxime (3) is obtained. Subsequently, it reacts with carboxylic acid or acid anhydride to obtain oxime ester (4). The reaction route is as follows:

[0017]

[0018] Alternatively, pseudo-taraxasterone (2) reacts with methoxylamine or benzyloxylamine under alkaline conditions to form oxime ether 5 or 6. The reaction route is as follows:

[0019]

[0020] Furthermore, the general structural formula II of the E-ring epoxy derivative of pseudo-taraxasterol is as follows:

[0021]

[0022] Among them, R is hydrogen, acetyl, propionyl, butyryl, benzoyl.

[0023] Furthermore, the preparation method of the E-ring epoxy derivative of pseudo-taraxasterol includes the following steps:

[0024] Using pseudo-taraxasterol (1) as the raw material, it reacts with acid anhydride or carboxylic acid to obtain the intermediate 7 protected by 3-position carboxylic acid ester. Then, it is oxidized by an oxidant such as meta-chloroperoxybenzoic acid (m-CPBA) to obtain pseudo-taraxasterol-20,21-epoxy-3-carboxylic acid ester (8). The reaction route is as follows:

[0025]

[0026] Furthermore, the E-ring derivative of pseudo-taraxasterol is a 21-position oxime derivative, and its general structural formula III is as follows:

[0027]

[0028] Among them, R2 is hydrogen, acetyl, propionyl, butyryl, benzoyl; R1 is oxime (=NOH), oxime carboxylic acid ester (=NOCOR’), where R’ is an alkyl group with 1-4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl, styrene and substituted styrene, carboxylic acid with 2-4 carbons; or R1 is oxime ether (=NOR’), where R’ is an alkyl group with 1-4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl.

[0029] Furthermore, the preparation method of the ketone and oxime derivatives of the E-ring of pseudo-taraxasterol includes the following steps:

[0030] Using pseudo-taraxasterol-20,21-epoxy-3-carboxylate (8) as a raw material, reacting with pyridinium hydrofluoride to obtain pseudo-taraxasterol-21-one-3-carboxylate (9), and then reacting with hydroxylamine hydrochloride, etc. to obtain the corresponding pseudo-taraxasterol-21-oxime-3-carboxylate (10), and then reacting with carboxylic acid or acid anhydride to obtain pseudo-taraxasterol-3-carboxylate-21-oxime ester (11). The reaction route is as follows:

[0031]

[0032] Furthermore, the structural formula of the 3-oxime derivative of the A-ring of pseudo-taraxasterol is one of the following:

[0033]

[0034] Alternatively, the structural formula of the 20-position and / or 21-position derivative of the E-ring of pseudo-taraxasterol is one of the following:

[0035]

[0036]

[0037] The application of the above-mentioned pseudo-taraxasterol A-ring and E-ring derivatives as and / or in the preparation of α-glucosidase inhibitors.

[0038] The application of the above-mentioned pseudo-taraxasterol A-ring and E-ring derivatives as and / or in the preparation of hypoglycemic drugs.

[0039] The advantages and positive effects achieved by the present invention are as follows:

[0040] 1. All the oxime derivatives of the A-ring and E-ring of pseudo-taraxasterol in the present invention are new compounds, and it is first discovered that this type of derivative has good α-glucosidase inhibitory activity and has the potential to be developed into a new hypoglycemic drug.

[0041] 2. The 21-oxime ether derivative (Compound 15) and 3-oxime succinate derivative (Compound 16) in the present invention have good α-glucosidase inhibitory activity, and their IC 50 is about 5 μM, which is about 45 times higher than the activity of the positive control drug acarbose (IC 50 = 230.60 μM), indicating that this series of compounds has good application prospects in hypoglycemia.

[0042] 3. The process for preparing the pseudo-taraxasterol derivatives obtained in the present invention is simple and has a high yield. The preparation of its derivatives does not require conditions such as anhydrous and anaerobic, and the reaction yield is high and the time used is short.

[0043] 4. Pseudo-taraxasterol is a natural product widely distributed in various plant-based foods or traditional Chinese medicines such as dandelions. It has high safety, but due to problems such as difficult separation and purification, there are very few reports on pseudo-taraxasterol, and the novelty of this invention is high.

[0044] 5. The A-ring and E-ring oxime derivatives of pseudo-taraxasterol synthesized in this invention have good activities. They can be used as lead compounds for new hypoglycemic drugs and can also be used as α-glucosidase inhibitors, showing the potential to be developed into new drugs. Description of the Drawings

[0045] Figure 1 1H NMR spectrum of Compound 3 in deuterated chloroform in this invention;

[0046] Figure 2 13C NMR spectrum of Compound 4 in deuterated chloroform in this invention;

[0047] Figure 3 1H NMR spectrum of Compound 5 in deuterated chloroform in this invention;

[0048] Figure 4 13C NMR spectrum of Compound 6 in deuterated chloroform in this invention;

[0049] Figure 5 1H NMR spectrum of Compound 7 in deuterated chloroform in this invention;

[0050] Figure 6 13C NMR spectrum of Compound 8 in deuterated chloroform in this invention;

[0051] Figure 7 1H NMR spectrum of Compound 10 in deuterated chloroform in this invention;

[0052] Figure 8 13C NMR spectrum of Compound 11 in deuterated chloroform in this invention;

[0053] Figure 9 1H NMR spectrum of Compound 12 in deuterated chloroform in this invention;

[0054] Figure 10 13C NMR spectrum of Compound 13 in deuterated chloroform in this invention;

[0055] Figure 11 1H NMR spectrum of Compound 14 in deuterated chloroform in this invention;

[0056] Figure 12 1H NMR spectrum of Compound 15 in deuterated chloroform in this invention;

[0057] Figure 13 1H NMR spectrum of Compound 16 in deuterated chloroform in this invention;

[0058] Figure 14 The IC 50 curve of the inhibitory activity of compound 15 against α-glucosidase in the present invention;

[0059] Figure 15 The IC 50 curve of the inhibitory activity of compound 16 against α-glucosidase in the present invention. Detailed implementation manners

[0060] The present invention will be further described below in conjunction with embodiments. The following embodiments are narrative and not restrictive, and the protection scope of the present invention cannot be limited by the following embodiments.

[0061] All kinds of experimental operations involved in the specific embodiments are conventional techniques in the art. For the parts not specifically noted in this article, those of ordinary skill in the art can refer to various common reference books, scientific and technological literatures or relevant specifications, manuals, etc. before the application date of the present invention for implementation.

[0062] A taraxasterol A-ring and E-ring derivative, wherein the taraxasterol A-ring derivative is a 3-position oxime derivative, and the taraxasterol E-ring derivative is a 20-position and / or 21-position epoxy, ketone and oxime derivative.

[0063] Preferably, the 3-position oxime derivative of the taraxasterol A-ring has the following general structural formula I:

[0064]

[0065] Among them, R at the 3-position is oxime (=NOH), oxime carboxylate (=NOCOR'), where R' is an alkyl group with 1-4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl, styrene and substituted styrene, a carboxylic acid with 2-4 carbons; or R is oxime ether (=NOR'), where R' is an alkyl group with 1-4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl.

[0066] Preferably, the preparation method of the 3-position oxime derivative of the taraxasterol A-ring includes the following steps:

[0067] Using taraxasterol (1) as a raw material, it is oxidized under conditions such as pyridinium chlorochromate (PCC) to obtain taraxasterone (2), and then the corresponding oxime (3) is obtained under conditions such as hydroxylamine hydrochloride (NH2OH.HCl), and then reacted with a carboxylic acid or acid anhydride to obtain an oxime ester (4). The reaction route is as follows:

[0068]

[0069] Alternatively, taraxasterone (2) reacts with methoxylamine or benzyloxylamine under alkaline conditions to form oxime ethers 5 or 6. The reaction route is as follows:

[0070]

[0071] Preferably, the general structural formula II of the E-ring epoxy derivative of pseudotaraxasterol is as follows:

[0072]

[0073] Wherein, R is hydrogen, acetyl, propionyl, butyryl, benzoyl.

[0074] Preferably, the preparation method of the E-ring epoxy derivative of pseudotaraxasterol comprises the following steps:

[0075] Using pseudotaraxasterol (1) as a raw material, reacting with an acid anhydride or a carboxylic acid to obtain an intermediate 7 protected by a 3-position carboxylic acid ester, and then oxidizing with an oxidant such as m-chloroperoxybenzoic acid (m-CPBA) to obtain pseudotaraxasterol-20,21-epoxy-3-carboxylic acid ester (8), and the reaction route is as follows:

[0076]

[0077] Preferably, the E-ring derivative of pseudotaraxasterol is a 21-position oxime derivative, and its general structural formula III is as follows:

[0078]

[0079] Wherein, R2 is hydrogen, acetyl, propionyl, butyryl, benzoyl; R1 is oxime (=NOH), oxime carboxylate (=NOCOR'), wherein R' is an alkyl group with 1 to 4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl, styrene and substituted styrene, a carboxylic acid with 2 to 4 carbons; or R1 is oxime ether (=NOR'), wherein, R' is an alkyl group with 1 to 4 carbons, phenyl and substituted phenyl, benzyl and substituted benzyl.

[0080] Preferably, the preparation method of the ketone and oxime derivatives of the E-ring of pseudotaraxasterol comprises the following steps:

[0081] Using pseudotaraxasterol-20,21-epoxy-3-carboxylic acid ester (8) as a raw material, reacting with hydrogen fluoride pyridine salt to obtain pseudotaraxasterol-21-one-3-carboxylic acid ester (9), and then reacting with hydroxylamine hydrochloride, etc. to obtain the corresponding pseudotaraxasterol-21-oxime-3-carboxylic acid ester (10), and then reacting with a carboxylic acid or an acid anhydride to obtain pseudotaraxasterol-3-carboxylic acid ester-21-oxime ester (11), and the reaction route is as follows:

[0082]

[0083] Preferably, the structural formula of the 3-position oxime derivative of the A-ring of pseudotaraxasterol is one of the following:

[0084]

[0085] Alternatively, the structural formula of the E-ring 20- and / or 21-position derivatives of pseudo-taraxasterol is one of the following:

[0086]

[0087]

[0088] Use of the pseudo-taraxasterol A-ring and E-ring derivatives as described above in the preparation of and / or as an α-glucosidase inhibitor.

[0089] Use of the pseudo-taraxasterol A-ring and E-ring derivatives as described above in the preparation of and / or as an antihyperglycemic drug.

[0090] Specifically, the related preparation and detection are as follows:

[0091] Example 1 Synthesis of Pseudo-taraxasterol-3-oxime (Compound 3)

[0092] The specific reaction route is as follows:

[0093]

[0094] The specific steps are as follows:

[0095] (1) Synthesis of Compound 2: Dissolve pseudo-taraxasterol (0.11 mmol) in 1.0 mL of dichloromethane, add pyridinium chlorochromate (PCC, 0.22 mmol), stir the reaction at room temperature for 1 h, and monitor by thin-layer chromatography (petroleum ether:acetone = 10:1, v / v. This ratio involved in the following examples is also v / v). When it is observed that the raw materials disappear, it is judged that the reaction is complete. Pour the reaction solution into dichloromethane (10.0 mL), extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 2 with a yield of 98.2%. 1 H NMR(400MHz,CDCl3)δ=5.26(d,J=6.8Hz,1H),2.39-2.54(m,2H),1.90-1.97(m,2H),1.63(s,3H),1.09(s,6H),1.03(s,4H),1.00(s,3H),0.95(s,6H),0.73(s,3H).

[0096] (2) Synthesis of Compound 3: Dissolve Compound 2 (0.1 mmol) in 1.0 mL of absolute ethanol, add hydroxylamine hydrochloride (0.1 mmol) and anhydrous sodium acetate (0.2 mmol). After stirring the reaction at 50 °C for 1 h, monitor by thin-layer chromatography (petroleum ether: acetone = 20:1). When the raw materials disappear, it is judged that the reaction is complete. Rotate the reaction solution to dryness, add dichloromethane (10.0 mL), extract with water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 3 with a yield of 98.0%. 1 1H NMR (400 MHz, CDCl3) δ = 5.26 (d, J = 6.8 Hz, 1H), 2.94 - 3.00 (m, 1H), 2.25 - 2.33 (m, 1H), 1.63 (s, 3H), 1.15 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H), 1.00 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.74 (s, 3H). 13 13C NMR (400 MHz, CDCl3) δ 167.5, 139.9, 119.03, 55.6, 50.2, 48.8, 42.5, 42.3, 41.2, 40.4, 39.4, 38.9, 37.3, 36.8, 36.5, 34.5, 34.0, 27.8, 27.5, 27.2, 23.1, 22.7, 22.1, 21.8, 19.2, 17.9, 17.3, 16.2, 16.1, 14.8. The spectra are as Figure 1 shown.

[0097] Example 2 Synthesis of Pseudotaraxasterol-3-oxime methyl ether (Compound 4)

[0098] The specific synthesis route is as follows:

[0099]

[0100] The specific steps are as follows:

[0101] Dissolve Compound 2 (0.05 mmol) in 1.0 mL of absolute ethanol, add methoxyamine hydrochloride (0.2 mmol) and anhydrous sodium acetate (0.2 mmol). After stirring the reaction at 80 °C for 12 h, monitor by thin-layer chromatography (petroleum ether: acetone = 20:1). When the raw materials disappear, it is judged that the reaction is complete. Evaporate the reaction solvent to dryness, extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 4 with a yield of 97.5%. 11H NMR (400 MHz, CDCl3) δ = 5.26 (d, J = 6.8 Hz, 1H), 3.81 (s, 3H), 2.83 - 2.90 (m, 1H), 2.19 - 2.27 (m, 1H), 1.63 (s, 3H), 1.25 (s, 3H), 1.14 (s, 3H), 1.07 (s, 3H), 1.04 (s, 3H), 0.93 (s, 6H), 0.74 (s, 3H). 13 13C NMR (400 MHz, CDCl3) δ 166.3, 139.9, 119.0, 61.2, 55.6, 50.1, 48.8, 42.5, 42.3, 41.2, 40.1, 39.4, 39.0, 37.2, 36.8, 36.5, 34.5, 34.0, 29.8, 27.8, 27.6, 27.1, 23.3, 22.7, 22.1, 21.8, 19.2, 17.9, 16.2, 16.1, 14.8. The spectrum is as Figure 2 shown.

[0102] Synthesis of Pseudo - taraxasterol - 3 - oxime benzyl ether (Compound 5) in Example 3

[0103]

[0104] Dissolve Compound 2 (0.06 mmol) in 1.0 mL of absolute ethanol, add O - (benzyl)hydroxylamine hydrochloride (0.12 mmol) and anhydrous sodium acetate (0.24 mmol), stir and react at 55 °C for 6 h, monitor by thin - layer chromatography (petroleum ether:acetone = 20:1), when the raw materials disappear, judge that the reaction is complete. Evaporate the reaction solvent to dryness, extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 5 with a yield of 53.8%. 1 1H NMR (400 MHz, CDCl3) δ = 7.28 - 7.30 (m, 3H), 7.18 - 7.24 (m, 2H), 5.19 (d, J = 6.8 Hz, 1H), 4.99 (s, 2H), 2.80 - 2.85 (m, 1H), 2.17 - 2.25 (m, 1H), 1.81 (d, J = 7.2 Hz, 2H), 1.56 (s, 3H), 1.07 (s, 3H), 0.99 (s, 3H), 0.96 (s, 6H), 0.86 (s, 3H), 0.82 (s, 3H), 0.66 (s, 3H). 1313C NMR (400 MHz, CDCl3) δ 166.8, 140.0, 138.8, 128.3, 128.2, 127.6, 119.0, 75.4, 55.5, 50.1, 48.8, 42.5, 42.3, 41.2, 40.2, 39.4, 38.9, 37.2, 36.8, 36.4, 34.5, 33.9, 27.8, 27.7, 27.1, 23.2, 22.7, 22.1, 21.8, 19.2, 18.2, 17.9, 16.2, 16.1, 14.8. The spectrum is as Figure 3 shown below.

[0105] Synthesis of Pseudo-taraxasteryl-3-oxime acetate (Compound 6) in Example 4

[0106]

[0107] The specific steps are as follows:

[0108] Dissolve Compound 3 (0.03 mmol) in 1.0 mL of pyridine, add acetic anhydride (0.06 mmol) at 0 °C, stir the reaction at room temperature for 12 h, monitor by thin-layer chromatography (petroleum ether:acetone = 10:1), observe the disappearance of the raw material, and judge that the reaction is complete. Pour the reaction solution into dilute hydrochloric acid (1 mol / L), extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 6 with a yield of 100.0%. 1 1H NMR (400 MHz, CDCl3) δ = 5.26 (d, J = 7.2 Hz, 1H), 2.81 - 2.87 (m, 1H), 2.39 - 2.47 (m, 1H), 2.18 (s, 3H), 1.63 (s, 3H), 1.25 (s, 3H), 1.24 (s, 3H), 1.13 (s, 3H), 1.07 (s, 3H), 0.99 (s, 3H), 0.94 (s, 6H), 0.74 (s, 3H). 13 13C NMR (400 MHz, CDCl3) δ 175.1, 170.1, 139.9, 119.0, 55.5, 50.2, 48.8, 42.5, 42.3, 41.2, 39.4, 39.2, 37.2, 36.8, 36.4, 34.5, 33.8, 29.8, 27.7, 27.6, 27.1, 22.8, 22.1, 21.8, 20.2, 19.7, 19.2, 17.9, 16.4, 16.1, 14.8. HRMS(+ESI-TOF) m / z: [M+K] + calcd. for C32 H 51 NO2520.3557, found 520.3487. As Figure 4 shown.

[0109] Synthesis of Pseudo - taraxasteryl - 3 - oxime benzoate (Compound 7) in Example 5

[0110]

[0111] The specific steps are as follows:

[0112] Dissolve Compound 3 (0.05 mmol) in 1.0 mL of dichloromethane. Add diisopropylcarbodiimide (DIC, 0.1 mmol), 4 - dimethylaminopyridine (DMAP, 0.03 mmol) and benzoic acid (0.1 mmol) at 0 °C. Stir the reaction at room temperature for 12 h, and monitor by thin - layer chromatography (petroleum ether: acetone = 20:1). When the raw materials disappear, it is judged that the reaction is complete. Quench the reaction by adding water, extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 7 with a yield of 75.4%. 1 HNMR (400 MHz, CDCl3) δ = 5.26 (d, J = 6.8 Hz, 1H), 2.92 - 2.98 (m, 1H), 2.54 - 2.60 (m, 1H), 1.63 (s, 3H), 1.33 (s, 3H), 1.26 (s, 3H), 1.21 (s, 3H), 1.08 (s, 3H), 0.99 (s, 3H), 0.95 (s, 3H), 0.74 (s, 3H). 13 C NMR (400 MHz, CDCl3) δ 176.7, 164.4, 139.9, 133.1, 129.9, 129.7, 128.6, 119.1, 55.5, 50.2, 48.8, 42.5, 42.3, 41.7, 41.2, 39.4, 39.3, 37.3, 36.8, 36.4, 34.5, 33.8, 29.8, 27.8, 27.1, 22.9, 22.7, 22.2, 21.8, 20.1, 19.2, 17.9, 16.5, 16.1, 14.8. The spectrum is as Figure 5 shown.

[0113] Synthesis of Pseudo - taraxasteryl - 3 - oxime cinnamate (Compound 8) in Example 6

[0114] The specific synthetic route is as follows:

[0115]

[0116] The specific steps are as follows:

[0117] Dissolve compound 3 (0.03 mmol) in 0.5 mL of dichloromethane, add diisopropylcarbodiimide (DIC, 0.06 mmol), 4-dimethylaminopyridine (DMAP, 0.02 mmol) and cinnamic acid (0.09 mmol). After stirring the reaction at room temperature for 24 h, monitor by thin-layer chromatography (petroleum ether: acetone = 10:1). When it is observed that the raw materials disappear, it is judged that the reaction is complete. Pour the reaction solution into dichloromethane (10.0 mL), extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 8 with a yield of 100.0%. 1 H NMR (400 MHz, CDCl3) δ = 7.78 (d, J = 16.4 Hz, 1H), 7.55 (m, 2H), 7.40 (t, J = 3.2 Hz, 3H), 6.59 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 6.8 Hz, 1H), 2.88 - 2.94 (m, 1H), 2.46 - 2.54 (m, 1H), 1.63 (s, 3H), 1.30 (s, 3H), 1.26 (s, 3H), 1.18 (s, 3H), 1.08 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H), 0.74 (s, 3H). 13 C NMR (400 MHz, CDCl3) δ 175.9, 165.4, 145.5, 139.9, 134.6, 130.5, 129.0, 128.3, 119.0, 116.5, 55.5, 50.2, 48.8, 42.5, 42.3, 41.6, 41.2, 39.4, 37.2, 36.8, 36.4, 34.5, 33.8, 29.8, 27.8, 27.6, 27.1, 22.9, 22.7, 22.2, 21.8, 19.9, 19.2, 17.9, 16.5, 16.1, 14.8. The spectra are as Figure 6 shown.

[0118] Synthesis of pseudo-taraxasterol-20,21-epoxy-3-acetate (Compound 10) in Example 7

[0119]

[0120] The specific steps are as follows:

[0121] (1) Synthesis of Compound 9: Pseudo-taraxasterol (0.06 mmol) was dissolved in 0.5 mL of pyridine. Acetic anhydride (0.12 mmol) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. After monitoring by thin-layer chromatography (petroleum ether:acetone = 10:1) and observing the disappearance of the starting material, the reaction was judged to be complete. The reaction solution was poured into dilute hydrochloric acid (1 mol / L), extracted with dichloromethane and water, and the organic phases were combined, washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4, filtered to remove the desiccant, the solvent was evaporated, and the crude product was separated and purified by silica gel column chromatography to obtain white solid 9 with a yield of 95.6%. 1 H NMR (400 MHz, CDCl3) δ = 5.26 (d, J = 6.4 Hz, 1H), 4.46 - 4.50 (m, 1H), 2.04 (s, 3H), 1.63 (s, 3H), 1.04 (s, 3H), 0.99 (s, 3H), 0.98 (s, 3H), 0.94 (s, 3H), 0.87 (s, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.73 (s, 3H).

[0122] (2) Synthesis of Compound 10: Compound 9 (0.06 mmol) was dissolved in 1.0 mL of dichloromethane. m-Chloroperoxybenzoic acid (0.18 mmol) was added, and the mixture was stirred at room temperature for 1 h. After monitoring by thin-layer chromatography (petroleum ether:acetone = 10:1) and observing the disappearance of the starting material, the reaction was judged to be complete. The reaction solution was poured into saturated sodium sulfite aqueous solution, extracted with dichloromethane and water, and the organic phases were combined, washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4, filtered to remove the desiccant, the solvent was evaporated, and the crude product was separated and purified by silica gel column chromatography to obtain white solid 10 with a yield of 100.0%. 1 H NMR (400 MHz, CDCl3) δ = 4.45 - 4.49 (m, 1H), 3.04 (d, J = 5.6 Hz, 1H), 2.04 (s, 3H), 1.31 (s, 3H), 1.12 (s, 3H), 1.01 (s, 3H), 0.86 (s, 6H), 0.83 (s, 3H), 0.82 (s, 3H), 0.78 (s, 3H). 1313C NMR (400 MHz, CDCl3) δ 171.1, 81.0, 61.3, 60.6, 55.4, 50.0, 45.9, 42.7, 42.5, 41.1, 39.6, 38.5, 37.9, 37.0, 36.5, 34.3, 34.1, 28.0, 27.8, 26.5, 23.8, 23.3, 21.6, 21.4, 19.1, 18.4, 18.3, 16.6, 16.5, 16.1, 14.5. HRMS(+ESI-TOF) m / z: [M + H2O]+ calcd. for C 32 H 52 O3502.4022, found 502.3950. As Figure 7 shown

[0123] Synthesis of Pseudotaraxasterol-21-oxo-3-acetate (Compound 11) in Example 8

[0124]

[0125] The specific steps are as follows:

[0126] Dissolve Compound 10 (0.05 mmol) in 1.0 mL of dichloromethane, add pyridinium hydrofluoride (0.5 mmol), stir the reaction at room temperature for 1 h, monitor by thin-layer chromatography (petroleum ether: acetone = 10:1), observe the disappearance of the raw material, and judge that the reaction is complete. Pour the reaction solution into ice water, extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 11 with a yield of 73.0%. 1 1H NMR (400 MHz, CDCl3) δ = 4.46 - 4.50 (m, 1H), 2.98 (t, J = 7.2 Hz, 1H), 2.24 (d, J = 18.8 Hz, 1H), 2.04 (s, 3H), 1.91 (d, J = 18.8 Hz, 1H), 1.25 (s, 3H), 1.15 (s, 3H), 1.05 (s, 3H), 0.95 (s, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (d, J = 6.8 Hz, 3H). 1313C NMR(400MHz,CDCl3)δ215.3,171.2,81.0,55.5,50.5,49.5,45.2,42.4,41.2,39.0,38.9,38.5,37.9,37.2,35.0,34.7,34.1,29.8,28.1,26.8,26.1,23.8,21.6,21.5,19.9,18.3,16.6,16.5,16.1,15.0,11.3.HRMS(+ESI-TOF)m / z:[M+H]+calcd.for C 32 H 52 O3485.3995,found485.3986. As Figure 8 shown

[0127] Synthesis of Pseudo-taraxasterol-21-oxime-3-acetate (Compound 12) in Example 9

[0128]

[0129] Compound 11 (0.04 mmol) was dissolved in 1.0 mL of absolute ethanol, hydroxylamine hydrochloride (0.04 mmol) and anhydrous sodium acetate (0.08 mmol) were added, and the mixture was stirred at 50 °C for 1 h. After monitoring by thin-layer chromatography (petroleum ether:acetone = 10:1), when the disappearance of the starting material was observed, the reaction was judged to be complete. The reaction solution was concentrated in vacuo, dichloromethane (10.0 mL) was added, and the mixture was extracted with water. The organic phases were combined, washed with saturated NaCl aqueous solution, dried over anhydrous Na2SO4, filtered to remove the desiccant, and the solvent was evaporated. The crude product was separated and purified by silica gel column chromatography to obtain white solid 12 with a yield of 77.0%. 1 1H NMR(400MHz,CDCl3)δ=4.46-4.50(m,1H),2.97(t,J=6.8Hz,1H),2.39(d,J=18.8Hz,1H),2.14(d,J=19.2Hz,1H),2.04(s,3H),1.25(s,3H),1.15(s,3H),1.04(s,3H),1.03(s,3H),0.93(s,3H),0.88(s,3H),0.85(s,3H),0.84(s,3H),0.71(d,J=6.8Hz,3H). 1313C NMR (400 MHz, CDCl3) δ 171.2, 162.3, 81.0, 55.5, 50.5, 49.2, 41.8, 41.1, 39.3, 39.1, 38.5, 37.9, 37.2, 35.4, 34.3, 34.1, 33.5, 29.8, 28.1, 26.8, 26.0, 23.8, 21.7, 21.5, 18.8, 18.3, 16.6, 16.5, 16.1, 15.0, 13.3. HRMS(+ESI-TOF) m / z: [M+H]+ calcd. for C 32 H 53 NO3500.4104, found 500.4096. As Figure 9 shown

[0130] Synthesis of Pseudo-taraxasterol-21-oxime acetate-3-acetate (Compound 13) in Example 10

[0131]

[0132] Dissolve Compound 12 (0.03 mmol) in 0.5 mL of pyridine, add acetic anhydride (0.06 mmol) at 0 °C, stir the reaction at room temperature for 12 h, monitor by thin-layer chromatography (petroleum ether: acetone = 10:1), observe the disappearance of the raw material, and judge that the reaction is complete. Pour the reaction solution into dilute hydrochloric acid (1 mol / L), extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter off the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 13 with a yield of 79.6%. 1 1H NMR (400 MHz, CDCl3) δ = 4.46 - 4.50 (m, 1H), 3.03 (t, J = 6.6 Hz, 1H), 2.44 (d, J = 18.8 Hz, 1H), 2.17 (s, 3H), 2.14 (d, J = 11.6 Hz, 1H), 2.04 (s, 3H), 1.10 (d, J = 6.4 Hz, 3H), 1.03 (s, 6H), 0.93 (s, 3H), 0.87 (s, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.76 (d, J = 6.4 Hz, 3H). 1313C NMR (400 MHz, CDCl3) δ 171.1, 170.3, 169.6, 81.0, 55.5, 50.5, 48.8, 42.9, 42.3, 41.1, 39.1, 39.0, 38.5, 37.9, 37.2, 36.8, 34.3, 34.1, 33.9, 28.1, 26.7, 26.1, 23.8, 21.6, 21.5, 21.4, 20.0, 19.2, 18.3, 16.6, 16.5, 16.1, 15.0, 13.1. HRMS (+ESI-TOF) m / z: [M+H2O]+ calcd. for C 34 H 55 NO4559.4237, found 559.4252. As Figure 10 shown.

[0133] Synthesis of Pseudo-taraxasteryl-21-oxime succinate-3-acetate (Compound 14) in Example 11

[0134]

[0135] Dissolve Compound 12 (0.04 mmol) in 1.0 mL of dichloromethane, add DMAP (0.03 mmol) and succinic anhydride (0.08 mmol), stir the reaction at room temperature for 24 h, monitor by thin-layer chromatography (petroleum ether: ethyl acetate = 3:1), observe the disappearance of the raw materials, and judge that the reaction is complete. Purify the crude product by silica gel column chromatography to obtain white solid 14 with a yield of 66.7%. 1 1H NMR (400 MHz, CDCl3) δ = 4.46 - 4.50 (m, 1H), 3.04 (t, J = 6.4 Hz, 1H), 2.75 - 2.79 (m, 4H), 2.44 (d, J = 18.0 Hz, 1H), 2.15 (d, J = 19.2 Hz, 1H), 2.05 (s, 3H), 1.25 (s, 3H), 1.03 (s, 6H), 0.94 (s, 3H), 0.88 (s, 3H), 0.85 (s, 9H). 1313C NMR (400 MHz, CDCl3) δ 177.0, 171.2, 170.9, 170.0, 81.1, 55.5, 53.6, 50.5, 48.8, 43.0, 42.3, 41.1, 39.1, 39.0, 38.5, 37.9, 37.2, 36.8, 34.3, 34.1, 33.9, 29.8, 28.9, 28.1, 26.7, 26.1, 23.8, 21.6, 21.5, 19.1, 18.3, 16.6, 16.5, 16.1, 15.0, 13.1. HRMS (+ESI-TOF) m / z: [M+H]+ calcd. for C 36 H 57 NO6600.4264, found 600.4244. As Figure 11 shown

[0136] Synthesis of Pseudotaraxasterol-21-oxime methyl ether-3-acetate (Compound 15) in Example 12

[0137]

[0138] Dissolve Compound 11 (0.03 mmol) in 1.0 mL of absolute ethanol, add methoxylamine hydrochloride (0.12 mmol) and anhydrous sodium acetate (0.12 mmol), stir and react at 80 °C for 12 h, monitor by thin-layer chromatography (petroleum ether:acetone = 20:1), observe that the raw materials disappear, and judge that the reaction is complete. Evaporate the reaction solvent to dryness, extract with dichloromethane and water, combine the organic phases, wash with saturated NaCl aqueous solution, dry the organic phase with anhydrous Na2SO4, filter to remove the desiccant, evaporate the solvent, and purify the crude product by silica gel column chromatography to obtain white solid 15 with a yield of 97.5%. 1 1H NMR (400 MHz, CDCl3) δ = 4.46 - 4.50 (m, 1H), 3.84 (s, 3H), 2.90 - 2.93 (m, 1H), 2.32 (d, J = 18.4 Hz, 1H), 2.05 (d, J = 18.4 Hz, 1H), 2.04 (s, 3H), 1.56 (s, 3H), 1.03 (s, 3H), 1.01 (s, 3H), 0.92 (s, 3H), 0.88 (s, 3H), 0.85 (s, 6H), 0.72 (d, J = 6.0 Hz, 3H). 1313C NMR (400 MHz, CDCl3) δ 171.1, 161.5, 81.1, 61.3, 55.6, 50.6, 49.1, 42.4, 42.2, 41.1, 39.3, 39.1, 38.6, 37.9, 37.2, 35.5, 34.4, 34.1, 33.7, 28.1, 26.8, 26.1, 23.8, 21.7, 21.6, 21.5, 18.9, 18.3, 16.6, 16.5, 16.1, 15.0, 13.3. The spectrum is as Figure 12 shown below.

[0139] Synthesis of Pseudo-taraxasteryl-3-oxime succinate (Compound 16) in Example 13

[0140]

[0141] Dissolve Compound 3 (0.04 mmol) in 1.0 mL of dichloromethane, add succinic anhydride (0.08 mmol) and DMAP (0.03 mmol), stir and react at room temperature for 12 h, monitor by thin layer chromatography (petroleum ether: ethyl acetate = 1:1), and when the raw materials disappear, judge that the reaction is complete. Directly perform silica gel column chromatography on the reaction solution for separation and purification to obtain white solid 16 with a yield of 99.0%. 1 1H NMR (400 MHz, CDCl3) δ = 9.72 (s, 1H), 5.26 (d, J = 6.4 Hz, 1H), 2.76 - 3.00 (m, 4H), 1.63 (s, 3H), 1.33 (s, 3H), 1.08 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.74 (s, 3H). 13 13C NMR (400 MHz, CDCl3) δ 175.7, 171.2, 169.3, 139.9, 119.0, 55.4, 55.0, 50.1, 50.0, 48.8, 47.5, 42.3, 41.2, 39.4, 37.3, 36.8, 36.4, 34.5, 28.3, 27.8, 27.7, 27.6, 27.1, 26.9, 22.7, 21.8, 21.2, 19.8, 19.2, 18.5, 17.9, 16.1, 14.8. As Figure 13 shown below.

[0142] α-Glucosidase Inhibition Experiment of Compounds 1 - 16 in Example 14

[0143] Weigh potassium dihydrogen phosphate and dipotassium hydrogen phosphate, and prepare a 50 mM buffer solution (pH = 6.8) with water. Dissolve α-glucosidase in the above buffer solution to prepare an enzyme solution with a concentration of 0.04 U / mL. The substrate 4-nitrophenyl-α-D-glucopyranoside (p-NPG) is also dissolved in the above buffer solution to prepare a 0.5 mM p-NPG substrate solution. Dissolve the test compound and positive control with dimethyl sulfoxide (DMSO) to the required concentration.

[0144] Divide the test system into a blank group, a control group, a compound blank group, and a compound test group. The specific grouping is as follows:

[0145] Table 1 α-Glucosidase reaction system

[0146]

[0147] In the above experimental steps, add the above reagents to a 96-well microplate in sequence, incubate at 37 °C for 5 minutes, add the substrate after incubation is completed, and continue to incubate for 30 minutes. Measure the absorbance value (OD) at 405 nm with an enzyme-labeling instrument. The inhibition calculation is as follows, as shown in Formula 1:

[0148]

[0149] In the above formula, OD4 is the absorbance value of the compound test group, OD3 is the absorbance value of the compound blank group, OD2 is the absorbance value of the control group, and OD1 is the absorbance value of the blank group. Each experiment is carried out in parallel 3 times under the same conditions, and each parallel experiment has 2 parallel replicates. The result obtained is the average value of the total number of times, and the error value SD between each data is obtained.

[0150] The inhibition results of the compound on α-glucosidase activity are shown in Table 2.

[0151] Table 2 Inhibition activity of the compound on α-glucosidase activity

[0152]

[0153] Note: a All results of α-glucosidase are the average value of three experiments ± SD; b Acarbose is used as the positive control.

[0154] Table 2 results show that natural pseudotaraxasterol 1 has good α-glucosidase inhibitory activity, but poor solubility. Therefore, in the present invention, its derivatives were prepared by derivatization. Oxidation was carried out at the 3-position of ring A (compound 2) or an oxime was prepared (compound 3). Further, the oxime was prepared into an oxime ether (compounds 4-5) or an oxime ester (compounds 6-8, 16). Among them, the oxime ester derivatives all have good activity, and the succinate ester has the highest activity (IC 50 = 5.21 μM), indicating that the introduction of an oxime ester on ring A can improve the activity. After oxidizing the 20,21-double bond, the activity decreased significantly (IC 50 > 50 μM for compound 10). After further converting the 20,21-epoxy group into a 21-ketone (compound 11), the activity increased (IC 50 = 14.75 μM). After further derivatizing the carbonyl group into an oxime (compound 12), the activity increased (IC 50 = 11.71 μM), slightly higher than that of pseudotaraxasterol. After further derivatizing the oxime into an oxime carboxylate, there were significant differences in activity. It is speculated that the derivatization at the 21-position into an oxime becomes an important site for binding to the enzyme, and the hydrogen bond donor (functional group with hydrogen) is an essential group for activity. Therefore, the oxime (compound 12) and the oxime succinate ester (compound 14) are beneficial to improving the activity, while the activity of compound 13 decreased. However, the oxime ether is helpful to improve the activity, such as compound 15 (IC 50 = 5.09 μM), which is 45 times more active than the positive control acarbose (IC 50 = 230.60 μM). Two representative compounds 15 and 16 were selected, and their IC 50 curves are shown in Figure 14 、 15 . Therefore, the synthesized pseudotaraxasterol ring A and ring E oxime derivatives of the present invention can be used as lead compounds for new hypoglycemic drugs and can also be used as α-glucosidase inhibitors, with the potential to be developed into new drugs.

[0155] In summary, the present invention for the first time found that the pseudotaraxasterol ring A and ring E derivatives have good α-glucosidase inhibitory activity. All derivatives are new compounds, and their activities were discovered for the first time. In addition, pseudotaraxasterol is a natural product, widely distributed in plant-based foods or traditional Chinese medicines, and has high safety. Therefore, the discovery of the new activities of pseudotaraxasterol and its derivatives has good practical application value.

[0156] Although the embodiments of the present invention are disclosed for illustrative purposes, those skilled in the art can understand that: without departing from the spirit and scope of the present invention and the appended claims, various substitutions, changes, and modifications are possible. Therefore, the scope of the present invention is not limited to the content disclosed in the embodiments.

Claims

1. A pseudotaraxasterol A-ring and E-ring derivative, characterized in that: The pseudotaraxasterol A ring derivative is a 3-position oxime derivative, and the pseudotaraxasterol E ring derivative is a 20-position and / or 21-position epoxy, ketone and oxime derivative.

2. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 1, characterized in that: The oxime derivative at the 3-position of the A ring of pseudotaraxasterol has the following general structural formula I: Among them, R at position 3 is oxime (=NOH), oxime carboxylate (=NOCOR'), wherein R' is an alkyl group having 1 to 4 carbon atoms, phenyl and substituted phenyl groups, benzyl and substituted benzyl groups, styrene and substituted styrene groups, or a carboxylic acid having 2 to 4 carbon atoms; or R is an oxime ether (=NOR'), wherein R' is an alkyl group having 1 to 4 carbon atoms, phenyl and substituted phenyl groups, benzyl and substituted benzyl groups.

3. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 2, characterized in that: The preparation method of the oxime derivative at position 3 of the A ring of pseudotaraxasterol comprises the following steps: Pseudotaraxasterol (1) is used as a raw material, and oxidized under pyridinium chlorochromate to obtain pseudotaraxasterone (2), which is then oxidized under hydroxylamine hydrochloride to obtain the corresponding oxime (3), which is then reacted with carboxylic acid or acid anhydride to obtain oxime ester (4). The reaction route is as follows: Alternatively, pseudotaraxasterone (2) reacts with methoxyamine or benzyloxyamine under alkaline conditions to generate oxime ether 5 or 6, and the reaction scheme is as follows:

4. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 1, characterized in that: The general structural formula II of the E-ring epoxy derivative of pseudotaraxasterol is as follows: Among them, R is hydrogen, acetyl, propionyl, butyryl, or benzoyl.

5. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 4, characterized in that: The preparation method of the pseudotaraxasterol E-ring epoxy derivative comprises the following steps: Pseudotaraxasterol (1) is used as a raw material and reacted with anhydride or carboxylic acid to obtain 3-position carboxylate-protected intermediate 7, which is then oxidized with m-chloroperbenzoic acid oxidant to obtain pseudotaraxasterol-20,21-epoxy-3-carboxylate (8). The reaction scheme is as follows:

6. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 1, characterized in that: The E-ring derivative of pseudotaraxasterol is a 21-oxime derivative, and its general structural formula III is as follows: Wherein, R2 is hydrogen, acetyl, propionyl, butyryl, benzoyl; R1 is oxime (=NOH), oxime carboxylate (=NOCOR'), wherein R' is an alkyl group having 1 to 4 carbon atoms, phenyl and substituted phenyl groups, benzyl and substituted benzyl groups, styrene and substituted styrene groups, or a carboxylic acid having 2 to 4 carbon atoms; or R1 is an oxime ether (=NOR'), wherein R' is an alkyl group having 1 to 4 carbon atoms, phenyl and substituted phenyl groups, benzyl and substituted benzyl groups.

7. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 6, characterized in that: The preparation method of the ketone and oxime derivatives of the E ring of pseudotaraxasterol comprises the following steps: Pseudotaraxacinol-20,21-epoxy-3-carboxylate (8) is used as a raw material, reacted with hydrogen fluoride pyridinium salt to obtain pseudotaraxacinol-21-keto-3-carboxylate (9), then reacted with hydroxylamine hydrochloride to obtain the corresponding pseudotaraxacinol-21-oxime-3-carboxylate (10), and then reacted with carboxylic acid or acid anhydride to obtain pseudotaraxacinol-3-carboxylate-21-oxime ester (11). The reaction scheme is as follows:

8. The pseudotaraxasterol A-ring and E-ring derivatives according to claim 1, characterized in that: The structural formula of the oxime derivative at position 3 of the A ring of pseudotaraxasterol is one of the following: Alternatively, the structural formula of the derivative at position 20 and / or 21 of the E ring of pseudotaraxasterol is one of the following:

9. Use of the A-ring and E-ring derivatives of pseudotaraxasterol according to any one of claims 1 to 8 as and / or in the preparation of α-glucosidase inhibitors.

10. Use of the A-ring and E-ring derivatives of pseudotaraxasterol according to any one of claims 1 to 8 as and / or in the preparation of hypoglycemic drugs.

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