Synthesis method and application of tetra-substituted pyran compound

Abstract

The invention provides a synthesis method and application of a tetra-substituted pyran compound. The tetra-substituted pyran compound is directly constructed through a one-pot cascade reaction under an organic base catalysis system by taking triketone olefin and allyl ammonium salt as key reaction raw materials. The method has the advantages that the operation is simple and convenient, no water or oxygen is needed, the reaction is efficient, the steps are simple, the method is environment-friendly, the reaction is easy to amplify, and the method has practical value. Activity tests prove that the compounds have certain inhibitory activity on alpha-glucosidase, or can be used for treating diabetes mellitus.

Description

Technical Field

[0001] This invention relates to a method for synthesizing tetrasubstituted pyran compounds and their application in pharmaceuticals. Background Technology

[0002] Pyrans, as an important oxygen-containing heterocyclic skeleton, are widely found in natural products and synthetic compounds. Their derivatives, due to their structural flexibility and functionality, are often used as intermediates in the synthesis of functional molecules and bioactive compounds. In the traditional synthetic routes for these compounds, intramolecular Michael addition is one of the classic methods: this reaction involves the simultaneous addition of oxygen-containing heterocyclic skeletons... α, β Starting with compounds containing unsaturated carbonyl groups and nucleophilic groups, a Michael addition reaction is first used to form an intermediate with a specific structure. Then, an intramolecular ring-closure reaction is used to construct the pyran ring skeleton, ultimately yielding pyran derivatives. Among these, polysubstituted pyrans have been reported to possess various biological activities, such as coumarins, anthocyanins, astragaloside A derivatives, and pyranoses. In particular, the polysubstituted pyran drug zanamivir was approved by the US FDA in August 1999 for the treatment of influenza A and B, and was the first neuraminidase inhibitor for the treatment of influenza-like viruses.

[0003]

[0004] Drugs and active molecules containing tetrasubstituted pyran compounds As scientists delve deeper into their research, more and more efficient synthetic strategies for tetrasubstituted pyrans have been developed. However, apart from synthetic routes such as transition metal catalysis, few organocatalytic strategies for synthesizing this framework have been reported. For example, in 2022, Zhang Wanbin's research group proposed copper-catalyzed synthesis of polysubstituted pyran compounds from alkynyl ketone imines and α-cyanoketones. Chem. Eur. J. 2022, 28, e202200128). In 2024, Yan Kelu's research group reported the synthesis of tetrasubstituted pyran compounds by the reaction of 3-oxo-4-pentenonitriles with alkynes under rhodium catalysis. Chin. J. Chem While the above strategies (e.g., 2024, 42, 1986-1992) employ various methods, they often involve high catalyst costs, stringent reaction requirements, and demanding conditions such as multi-step reactions and high temperatures. Therefore, efficiently constructing a tetrasubstituted pyran skeleton under mild conditions remains a challenging task. The objective of this invention is to design a simple and practical catalytic method to prepare this skeleton, synthesizing tetrasubstituted pyran compounds from inexpensive and readily available raw materials via base catalysis. This aims to address the problems of cumbersome steps, low atom utilization, high reagent costs, and insufficient environmental friendliness in the synthesis of existing pyran compounds, providing a new pathway for the efficient preparation and pharmaceutical applications of these compounds. Summary of the Invention

[0005] This invention innovatively realizes a highly efficient method for synthesizing tetrasubstituted pyran skeletons. The inventors discovered that triketones are a unique class of compounds containing multiple carbonyl substitutions, possessing characteristics such as stability and ease of preparation. Therefore, this invention designs a method for the efficient preparation of tetrasubstituted pyran compounds using triketones and allyl ammonium salts as reactants under organic base catalysis.

[0006] The synthesis reaction of this invention includes the following steps: Triketene, allyl ammonium salt, and solvent are added to a reaction flask and stirred to fully dissolve the solid raw materials. Then, an organic base is added as a catalyst, and the reaction is carried out at a constant temperature of 40-60 °C with stirring for 5-6 hours. After the reaction is completed as detected by TLC, the organic phase is extracted and collected. The solvent is removed by vacuum distillation to obtain the crude product. Finally, using petroleum ether / ethyl acetate solution as the mobile phase, the tetrasubstituted pyran compound is obtained by column chromatography. The reaction formula is as follows:

[0007] Among them, R 1 Selected from any one of hydrogen, bromine, fluorine, methyl, and methoxy; R 2 Selected from methyl or phenyl; R 3 It is selected from methyl or diphenylmethyl.

[0008] As shown in reaction formula (a) above, the present invention uses the triketone olefin shown in formula (I) and the allyl ammonium salt shown in formula (II) as reaction raw materials to react under the catalysis of an organic base to obtain a tetrasubstituted pyran compound as shown in formula (III).

[0009] In this invention, the organic base catalyst is DIPEA, Cs2CO3, Et3N, or DABCO. Et3N is preferred as the organic base catalyst.

[0010] In this invention, the solvent is MeCN, Toluene, DCM, THF, or CHCl3. MeCN is the preferred solvent.

[0011] In this invention, the molar ratio of the reactants—triketone olefin, allyl ammonium salt, and catalyst—is 1.0:1.2-2:0.1-0.3. Preferably, the ratio of the two is 1:1.2:0.2.

[0012] In this invention, the reaction temperature is 40-60 ℃; preferably, the temperature is 50 ℃.

[0013] The present invention utilizes mild conditions and achieves a high yield. Furthermore, the one-pot tandem reaction shortens the reaction process, improving production efficiency and reducing costs. Finally, the tetrasubstituted pyran compounds exhibit some inhibitory activity against α-glucosidase, potentially making them suitable for diabetes treatment research.

[0014] This invention proposes the preparation of tetrasubstituted pyran compounds as shown in formula (III) using the above-described synthetic method.

[0015] Among them, R 1 Selected from any one of hydrogen, bromine, fluorine, methyl, and methoxy; R 2 Selected from methyl or phenyl; R 3 It is selected from methyl or diphenylmethyl.

[0016] This invention uses triketene and allyl ammonium salt as reactants, and obtains a series of tetrasubstituted pyran compounds via a one-pot tandem reaction under the catalysis of an organic base (such as Et3N). The advantages of this invention include: simple operation, no need for anhydrous and oxygen-free conditions, high reaction efficiency, concise steps, environmental friendliness, easy scale-up, and practical value. While cathodic drugs (such as acarbose) have a glycosylated structure, the tetrasubstituted pyran compounds of this invention represent a novel skeletal type, and the tetrasubstituted sites can be further enhanced through structural derivatization. Compared to cathodic drugs, which are easily degraded by enzymes, the tetrasubstituted pyran compounds of this invention exhibit greater metabolic stability, prolonging their in vivo duration of action and improving bioavailability. Attached Figure Description

[0017] Figure 1 This is the hydrogen spectrum of compound 1.

[0018] Figure 2 This is the carbon spectrum of compound 1.

[0019] Figure 3 This is the hydrogen spectrum of compound 2.

[0020] Figure 4 This is the carbon spectrum of compound 2.

[0021] Figure 5 This is the hydrogen spectrum of compound 3.

[0022] Figure 6 This is the carbon spectrum of compound 3.

[0023] Figure 7 This is the hydrogen spectrum of compound 4.

[0024] Figure 8 This is the carbon spectrum of compound 4.

[0025] Figure 9 This is the hydrogen spectrum of compound 5.

[0026] Figure 10 This is the carbon spectrum of compound 5.

[0027] Figure 11This is the hydrogen spectrum of compound 6.

[0028] Figure 12 This is the carbon spectrum of compound 6.

[0029] Figure 13 This is the hydrogen spectrum of compound 7.

[0030] Figure 14 This is the carbon spectrum of compound 7.

[0031] Figure 15 This is the hydrogen spectrum of compound 8.

[0032] Figure 16 This is the carbon spectrum of compound 8. Detailed Implementation

[0033] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention is not limited to the following embodiments. Variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention and are protected by the appended claims. The processes, conditions, reagents, experimental methods, etc., for implementing the present invention, except as specifically mentioned below, are all common knowledge and general knowledge in the art, and the present invention does not have any particular limitations. The data given in the following embodiments include specific operations, reaction conditions, and products. Product purity was determined by NMR. The reaction for synthesizing tetrasubstituted pyran compounds according to the present invention includes the following steps: As shown in equation a: Triketene, allyl ammonium salt, Et3N, and acetonitrile were added to a reaction vessel and stirred at 50 °C for 6 hours to obtain the tetrasubstituted pyran compound shown in formula (III). The product was then concentrated, neutralized, and separated by column chromatography. Condition screening was performed during the process, as shown in the table below:

[0034]

[0035] The reaction condition screening experiment showed that the optimal reaction conditions for obtaining tetrasubstituted pyran compounds were Et3N as catalyst, MeCN as solvent, and a temperature of 50 °C.

[0036] The tetrasubstituted pyran compounds shown in Table 1 are all products synthesized by the method of this invention.

[0037]

[0038] Example 1

[0039] After adding 3-acetyl-1-phenylpent-2-en-1,4-dione (21.6 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 1 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 83%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.84 (d, J = 7.2 Hz, 2H), 7.50 (t, J = 7.3 Hz, 1H), 7.43 (t, J = 7.4 Hz, 2H), 5.43 (q, J = 6.5 Hz, 1H), 3.42(s, 3H), 2.35 (s, 3H), 2.27 (s, 3H), 1.50 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100MHz, Chloroform- d ) δ 195.1, 194.9, 167.8, 163.7, 142.6, 137.6, 132.4, 128.4, 127.7, 117.4, 116.3, 71.9, 51.7, 31.2, 21.7, 17.9. Example 2

[0040] After adding 3-acetyl-1-(4-fluorophenyl)pent-2-en-1,4-dione (23.4 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. oThe mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 2 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 71%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.84 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 5.43 (q, J = 6.5 Hz, 1H), 3.46 (s, 3H), 2.35 (s, 3H), 2.29 (s, 3H), 1.49 (d, J = 6.5 Hz, 3H). 13 C{1H} NMR (100 MHz, Chloroform- d ) δ 194.8, 193.6, 165.1 (d, J = 252.0 Hz,), 163.6, 142.5, 134.25, 134.22, 130.1 (d, J = 9.0 Hz), 116.8 (d, J = 97.0 Hz), 115.5 (d, J = 22.0 Hz), 71.9, 51.8, 31.1,21.7, 17.9. 19 F{ 1 H} NMR (376 MHz, Chloroform- d ) δ -106.9. Example 3

[0041] After adding 3-acetyl-1-(4-bromophenyl)pent-2-en-1,4-dione (29.4 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. oThe mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 3 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 75%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.69 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 5.44 (q, J = 6.5 Hz, 1H), 3.47 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H), 1.49 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ 194.6, 194.1, 163.6, 142.5, 136.7, 131.7, 129.1, 127.2, 117.3, 116.5, 72.0, 51.8, 31.1, 21.8, 17.9. Example 4

[0042] After adding 3-acetyl-1-(4-methoxyphenyl)pent-2-en-1,4-dione (24.6 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 4 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 80%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.79 (d, J =8.3 Hz, 2H), 6.90 (d, J = 9.1 Hz, 2H), 5.40 (q, J= 6.5 Hz, 1H), 3.83 (s, 3H), 3.44 (s, 3H), 2.29 (s, 3H), 2.22 (s, 3H), 1.47 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ 195.5, 193.9, 166.9, 163.8, 163.0, 142.5, 130.7, 130.0, 117.1, 115.9, 113.7, 71.8, 55.3, 51.6, 31.3, 21.3, 17.8. Example 5

[0043] After adding 3-acetyl-1-(4-methylphenyl)pent-2-en-1,4-dione (23.0 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 5 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 71%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.73 (d, J =7.8 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 5.42 (q, J = 6.5 Hz, 1H), 3.44 (s, 3H), 2.38 (s, 3H), 2.32 (s, 3H), 2.24 (s, 3H), 1.49 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ195.2, 194.9, 167.4, 163.8, 143.2, 142.7, 135.2, 129.3, 127.9, 117.3, 116.1, 71.9, 51.7, 31.3, 21.7, 21.6, 17.9. Example 6

[0044] After adding 2-benzoyl-1,4-diphenylbut-2-en-1,4-dione (34.0 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 6 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 81%; 1 H NMR (400 MHz, Chloroform- d ) δ 8.01 – 7.94 (m,2H), 7.56 – 7.45 (m, 5H), 7.36 (d, J = 7.0 Hz, 2H), 7.20 (t, J = 7.4 Hz, 2H),7.14 – 7.04 (m, 4H), 5.80 (q, J = 6.5 Hz, 1H), 3.52 (s, 3H), 1.82 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ 195.0, 192.9, 163.7, 144.1, 138.1, 137.6, 132.9, 132.7, 132.3, 131.5, 130.2, 129.4, 128.5, 128.1, 128.0, 127.8, 116.4, 113.9, 72.3, 51.8, 18.0. Example 7

[0045] After adding 3-acetyl-1-phenylpent-2-en-1,4-dione (21.6 mg, 0.1 mmol), allyl diphenyl methyl ester ammonium salt (51.7 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 7 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 74%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.73 (d, J = 6.9 Hz,2H), 7.49 – 7.42 (m, 1H), 7.32 (d, J = 7.6 Hz, 2H), 7.23 – 7.16 (m, 5H), 7.05 –6.98 (m, 2H), 6.94 (m, 2H), 6.74 (s, 1H), 5.52 (q, J = 6.5 Hz, 1H), 2.32 (s,3H), 2.25 (s, 3H), 1.50 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ 195.2, 194.6, 167.5, 162.6, 142.4, 139.3, 139.2, 137.3, 132.5, 128.4, 128.28, 128.26, 128.1, 127.73, 127.69, 127.1, 127.0, 117.2, 115.8, 78.4, 72.1, 31.2, 21.6, 17.9. Example 8

[0046] After adding 3-acetyl-1-(thien-2-yl)pent-2-en-1,4-dione (22.2 mg, 0.1 mmol), allyl methyl ester ammonium salt (33.5 mg, 0.12 mmol, 1.2 equiv.), and acetonitrile (1.0 mL) to the reaction tube, Et3N (2 mg, 0.02 mmol, 0.2 equiv.) was added, and the mixture was stirred at 50 °C. o The mixture was stirred at temperature C for 6 hours. After the reaction was completed, the organic phase was collected by extraction using TLC. The solvent was removed by vacuum distillation, and the product 8 was obtained by column chromatography (eluent polarity: petroleum ether / ethyl acetate 12:1). Yield: 85%; 1 H NMR (400 MHz, Chloroform- d ) δ 7.59 (d, J = 4.9 Hz, 1H), 7.46 (d, J = 3.5 Hz, 1H), 7.09 – 7.02 (m, 1H), 5.39 (q, J = 6.5 Hz, 1H), 3.49 (s, 3H), 2.31 (s, 3H), 2.26 (s, 3H), 1.47 (d, J = 6.5 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, Chloroform- d ) δ 187.2,163.7, 144.7, 141.5, 132.9, 131.7, 127.9,116.7, 97.9, 71.9, 51.8, 31.3, 21.4, 17.8. Activity evaluation In vitro inhibitory activity assay of tetrasubstituted pyran compounds against α-glucosidase. The in vitro inhibitory activity of the enzyme α-glucosidase used in this invention was tested by examining the inhibitory activity of multiple compounds against α-glucosidase; acarbose was a positive resultant.

[0047] In vitro inhibitory activity of α-glucosidase was investigated, and the inhibitory activity of multiple compounds on α-glucosidase was detected. The experiment was divided into four groups: enzyme activity group (α-glucosidase solution and buffer solution), enzyme blank group (buffer solution and sample), positive group (α-glucosidase solution and positive drug solution), positive blank group (buffer solution and positive drug solution), sample group (α-glucosidase solution and sample), and sample blank group (buffer solution and sample). We conducted corresponding studies for each of these groups.

[0048] First: Preparation of the reaction solution. Accurately weigh 1 mg of compounds (1-8) and the positive control drug acarbose using an analytical balance, and transfer them to 1.5 mL centrifuge tubes respectively. Add DMSO according to the calculated volume using a standard pipette, and sonicate until completely dissolved to obtain a 10 mmol / L stock solution. Then perform a gradient dilution with DMSO to obtain a concentration gradient of 90, 30, and 10 μM for the compounds. Then, mix the above DMSO gradient solutions with PBS buffer (0.1 mol / L, pH=6.8).

[0049] Second: Accurately measure 15 μL of sample and 45 μL of α-glucosidase solution (0.3 μL / mL) using a standard pipette and add them to a 96-well plate. Shake and mix for 4 minutes to ensure complete mixing. Then preheat at 37°C, add 20 μL of substrate (PNPG) solution, shake and mix thoroughly, and react at 37°C for half an hour. Third: Add 100 μl of Na₂CO₃ solution to terminate the reaction. Finally, the inhibitory activity of the sample is determined by measuring the absorbance (OD) at 405 nm. By performing a regression equation on different concentrations of inhibitor and their corresponding inhibition rates, the half-maximal inhibitory concentration (IC₀) can be obtained. 50 ).

[0050] Cell viability was determined using the following formula: (1 - Δsample / Δenzyme) × 100%.

[0051] Sample A: Average OD value of the sample group; Blank A: Average OD value of the blank sample group (sample solution + PBS + DMSO + Na2CO3 solution, no enzyme, no substrate); Δsample = Sample A - Blank A.

[0052] A enzyme: Average OD value of the enzyme activity group (PBS + DMSO + enzyme + substrate + Na2CO3 solution); A enzyme blank: Average OD value of the substrate blank group. Δenzyme = A enzyme - A enzyme blank.

[0053] IC50 of the positive drug acarbose 50 Measurement results

[0054] OD measurement results of enzyme activity group and blank group

[0055] Table 1: Results of compound determination .

Claims

1. A tetrasubstituted pyran compound, characterized in that, The structure of the compound is shown in formula (Ⅲ): Among them, R 1 Selected from any one of hydrogen, bromine, fluorine, methyl, and methoxy; R 2 Selected from methyl or phenyl; R 3 It is selected from methyl or diphenylmethyl.

2. The method for synthesizing pyran compounds according to claim 1, characterized in that, Using triketene and allyl ammonium salt as reactants, a pyran compound as shown in formula (III) is obtained in a reaction solvent under the catalysis of an organic base; the reaction process is shown in reaction formula (a): Among them, R 1 Selected from any one of hydrogen, bromine, fluorine, methyl, and methoxy; R 2 Selected from methyl or phenyl; R 3 It is selected from methyl or diphenylmethyl.

3. The synthesis method according to claim 2, characterized in that, The alkali is any one or a combination of DIPEA, Cs2CO3, Et3N, and DABCO.

4. The synthesis method according to claim 2, characterized in that, The solvent is any one or a combination of MeCN, Toluene, DCM, THF, and CHCl3.

5. The synthesis method according to claim 2, characterized in that, The molar ratio of the reactants, triketene, allyl ammonium salt, and catalyst in the reaction is 1.0:1.2-2:0.1-0.

3.

6. The synthesis method according to claim 2, characterized in that, The reaction temperature is 40-60 ℃.

7. An α-glucosidase inhibitor, characterized in that, Includes the tetrasubstituted pyran compound as described in any one of claims 1 or the tetrasubstituted pyran compound prepared by the method described in any one of claims 2-6.

8. A drug for treating diabetes, characterized in that, Includes the tetrasubstituted pyran compound as described in any one of claims 1 or the tetrasubstituted pyran compound prepared by the method described in any one of claims 2-6.

9. A pharmaceutical composition for treating diabetes, characterized in that, Includes the tetrasubstituted pyran compound as described in any one of claims 1 or the tetrasubstituted pyran compound prepared by the method described in any one of claims 2-6.

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