阅读说明：本技术 一种苯并吡喃类化合物及其制备方法与应用 (Benzopyran compound and preparation method and application thereof ) 是由 周学明 林芳霞 陈光英 杨静雨 宋鑫明 李小宝 易继凌 于 2020-06-30 设计创作，主要内容包括：本发明公开了一种苯并吡喃类化合物,其结构通式如下：<Image he="385" wi="566" file="DDA0002561444920000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中R<Sub>1</Sub>、R<Sub>2</Sub>、R<Sub>3</Sub>、R<Sub>4</Sub>、R<Sub>5</Sub>、R<Sub>6</Sub>、R<Sub>7</Sub>、R<Sub>8</Sub>、R<Sub>9</Sub>、R<Sub>10</Sub>、R<Sub>11</Sub>分别为羟基、甲氧基或氢中的一种。本发明还公开了优选化合物的制备方法和其在制备抗类风湿关节炎药物中的应用。本发明首次发现了上述苯并吡喃类化合物在抑制类风湿关节炎滑膜细胞增殖中的活性,可用于制备抗类风湿关节炎的药物。(The invention discloses a benzopyran compound, which has the following structural general formula: wherein R is 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 Respectively one of hydroxyl, methoxyl or hydrogen. The invention also discloses a preparation method of the optimized compound and application of the optimized compound in preparing a medicament for resisting rheumatoid arthritis. The invention discovers that the benzopyran compound can inhibit the proliferation of synovial cells of rheumatoid arthritis for the first timeCan be used for preparing the medicine for resisting rheumatoid arthritis.)

1. A benzopyran compound has a structural general formula as follows:

wherein R is₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Respectively one of hydroxyl, methoxyl or hydrogen.

2. The benzopyran-based compound according to claim 1, wherein R is selected from the group consisting of₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Respectively, hydroxyl or hydrogen, and the number of the hydroxyl is 3.

3. The benzopyran-based compound according to claim 2, characterized in that the structural formula is as follows:

4. the process for producing benzopyran-based compounds according to claim 3, characterized by comprising the steps of:

(1) preparation of Fissistigma Oldhamii extract

Cold soaking or hot extracting dry stem of Fissistigma Oldhamii with ethanol solution to obtain extractive solution, and concentrating under reduced pressure to obtain Fissistigma Oldhamii extract;

(2) separating and purifying

Diluting the Fissistigma Oldhamii extract with water to obtain suspension, sequentially extracting with petroleum ether and ethyl acetate, concentrating the ethyl acetate extractive solution under reduced pressure to obtain extract, and separating by column chromatography, thin layer chromatography, molecular sieve chromatography, and high performance liquid chromatography to obtain the target compound.

5. The method for preparing benzopyran compounds according to claim 4, characterized in that in the step (1), the volume concentration of the ethanol solution is 30-95%; in the step (1) and the step (2), the concentration is carried out under reduced pressure, the temperature is 30-70 ℃, and the pressure is-0.06 to-0.15 MPa.

6. The process for producing benzopyran-based compounds according to claim 4 or 5, wherein in step (2), the column chromatography conditions are: loading the mixture to a 200-300-mesh silica gel column, and taking an ethyl acetate-petroleum ether mixed solvent with the ethyl acetate volume percentage of 30% as an eluent; the thin layer chromatography conditions are as follows: the developing solvent is ethyl acetate-petroleum ether mixed solvent with 50 percent of ethyl acetate volume percentage.

7. The process for producing benzopyran compounds according to claim 6, wherein in the step (2), the molecular sieve chromatography conditions are as follows: the molecular sieve is Sephadex LH-20, and chloroform-methanol mixed solvent with 50% chloroform volume percentage is used as eluent.

8. The method for preparing benzopyran compounds according to claim 7, characterized in that in the step (2), the eluent of the high performance liquid phase is acetonitrile and water with a volume ratio of 2: 3.

9. Use of a benzopyran compound according to any one of claims 1 to 3 for the preparation of a medicament against rheumatoid arthritis.

10. Use of a benzopyran compound according to any one of claims 1 to 3 for the preparation of a medicament for inhibiting the proliferation of synovial cells of rheumatoid arthritis.

Technical Field

The invention relates to the technical field of phytochemistry, in particular to a benzopyran compound and a preparation method and application thereof.

Background

Fissistigma Oldhamii (Fissistigma titentangense Tsiang et al T.Li) is a plant of Fissistigma Oldhamii of Annonaceae. The plant can be used as medicine, and its stem and leaf can be used for treating fracture and edema, and its whole plant can be used for treating rheumatalgia, deadlimb, etc. The fissistigma angustifolia contains a large amount of compounds, and a new-structure compound with obvious drug effect needs to be extracted urgently, so that the medicinal value of the fissistigma angustifolia is fully exerted.

Disclosure of Invention

The invention aims to provide a benzopyran compound which is extracted and separated from fissistigma angustifolia and has a new structure, has the activity of inhibiting the proliferation of synovial cells of rheumatoid arthritis, and can be applied to the preparation of drugs for resisting rheumatoid arthritis.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows:

a benzopyran compound has a structural general formula as follows:

wherein R is₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Each is one of hydroxyl, methoxyl or hydrogen, namely each is independently selected from-OH or-OMe or-H.

The compounds of the above structure can be obtained by organic synthesis.

Further, said R₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Respectively, hydroxyl or hydrogen, and the number of the hydroxyl is 3.

The benzopyran compound preferably has the following structural formula:

the preparation method of the preferred benzopyran compound comprises the following steps:

(1) preparation of Fissistigma Oldhamii extract

Cold soaking or hot extracting dry stem of Fissistigma Oldhamii with ethanol solution to obtain extractive solution, and concentrating under reduced pressure to obtain Fissistigma Oldhamii extract;

(2) separating and purifying

Diluting the Fissistigma Oldhamii extract with water to obtain suspension, sequentially extracting with petroleum ether and ethyl acetate, concentrating the ethyl acetate extractive solution under reduced pressure to obtain extract, and separating by column chromatography, thin layer chromatography, molecular sieve chromatography, and high performance liquid chromatography to obtain target compound named as fisigense A.

Further, in the step (1), the volume concentration of the ethanol solution is 30-95%, preferably 70-80%, and more preferably 75%.

Further, in the step (1), the vacuum concentration is carried out at the temperature of 30-70 ℃ and the pressure of-0.06 to-0.15 MPa; the preferred temperature is 40-55 ℃, and the preferred pressure is-0.09 to-0.1 MPa; more preferably, the temperature is 45 ℃ and the pressure is-0.095 MPa.

Further, in the step (2), the column chromatography conditions are as follows: and (3) loading the mixture to a 200-300-mesh silica gel column, wherein an ethyl acetate-petroleum ether mixed solvent with the ethyl acetate volume percentage of 30% is used as an eluent.

Further, in the step (2), the thin layer chromatography conditions are as follows: the developing solvent is ethyl acetate-petroleum ether mixed solvent with 50 percent of ethyl acetate volume percentage.

Further, in the step (2), the molecular sieve chromatography conditions are as follows: the molecular sieve is SephadexLH-20, and chloroform-methanol mixed solvent with chloroform volume percentage of 50% is used as eluent.

Further, in the step (2), the eluent of the high-performance liquid phase is acetonitrile and water with a volume ratio of 2: 3.

The benzopyran compound disclosed by the invention is applied to preparation of anti-rheumatoid arthritis medicines.

The benzopyran compound disclosed by the invention is applied to preparation of a medicament for inhibiting rheumatoid arthritis synovial cell proliferation. Wherein, the synoviocytes are primary rat synoviocytes.

Compared with the prior art, the invention has the beneficial effects that: the benzopyran compound with a new structure is extracted and separated from the fissistigma angustifolia, and the activity of the benzopyran compound in inhibiting the proliferation of synovial cells of rheumatoid arthritis is found for the first time, so that the benzopyran compound can be used for preparing the anti-rheumatoid arthritis medicament.

Drawings

FIG. 1 is a hydrogen spectrum of a benzopyran compound fisigense A according to example 1 of the present invention.

FIG. 2 is a carbon spectrum of a benzopyran compound fisigense A according to example 1 of the present invention.

Detailed Description

In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.

The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.

The materials, reagents and the like used in the examples of the present invention can be obtained commercially without specific description.

A benzopyran compound has a structural general formula as follows:

wherein R is₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Respectively one of hydroxyl, methoxyl or hydrogen. Preferably, said R is₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁Respectively, hydroxyl or hydrogen, and the number of the hydroxyl is 3. The compounds of the above structure can be obtained by organic synthesis. The benzopyran compound with the following structure is obtained by extracting and separating from fissistigma angustifolia: