阅读说明：本技术 一种辣椒素酯类化合物、其药学上可接受的盐及其制备方法和应用 (Capsinoid compound, pharmaceutically acceptable salt thereof, and preparation method and application thereof ) 是由 刘晓艳 龚云 杨秀伟 赵威 于 2019-09-09 设计创作，主要内容包括：本发明提供了一种辣椒素酯类化合物、其药学上可接受的盐及其制备方法和应用。该辣椒素酯类化合物的结构为首次报道,并且其来源于鸡血藤,可以作为鸡血藤中辣椒素酯类物质鉴别的标准品。本发明提供的辣椒素酯类化合物是从鸡血藤正品的乙酸乙酯萃取物中分离得到,意外地,我们还发现该化合物具有良好的镇痛效果,有望作为一种镇痛药物。(The invention provides a capsaicine ester compound, pharmaceutically acceptable salts thereof, and a preparation method and application thereof. The structure of the capsinoid compound is reported for the first time, and the capsinoid compound is derived from caulis spatholobi and can be used as a standard substance for identifying capsinoid substances in the caulis spatholobi. The capsaicine ester compound provided by the invention is separated from the ethyl acetate extract of the quality caulis Spatholobi, and surprisingly, the compound is also found to have good analgesic effect and is expected to be used as an analgesic drug.)

1. A capsinoid compound and a pharmaceutically acceptable salt thereof are characterized in that the capsinoid compound has a structural formula shown as a formula (I):

the pharmaceutically acceptable salt of the capsaicine ester compound has a structural formula shown as a formula (II):

m is an alkali metal or an alkaline earth metal, and n is 1 or 2.

2. The method for preparing capsinoid compound according to claim 1, comprising the steps of:

s1, adding water into a caulis spatholobi certified medicinal material, performing reflux extraction, concentrating, and drying to obtain a caulis spatholobi dry extract;

s2, dissolving the caulis Spatholobi dry extract obtained in the step S1 with water, and extracting with ethyl acetate to obtain an ethyl acetate extract;

s3, chloroform is used: eluting S2 on a silica gel column by using a system with the methanol volume ratio of (70-90): 1, and obtaining an ethyl acetate extract to obtain a component Fr.1;

s4.Fr.1 is subjected to silica gel chromatography, chloroform-methanol is sequentially subjected to gradient elution by a ratio system of 60:1, (50-40): 1, (30-20): 1 and 10:1, and a component obtained by collecting the ratio of 10:1 is named as Fr.1-4;

s5.Fr.1-4 is detected by TLC and HPLC, RP-SP-HPLC is adopted to sequentially adopt acetonitrile with the volume ratio of 2:3, 11:9 and 4: 1: eluting in a water system, and collecting components obtained by eluting at a ratio of 4:1, namely Fr.1-4-3, and then adding acetonitrile at a volume ratio of (40-50) to (60-50): combining an aqueous solvent with RP-SP-HPLC to obtain the capsaicine ester compound.

3. The preparation method according to claim 2, wherein in S1, the mass ratio of the caulis Spatholobi to water is 1: 5.

4. The method according to claim 2, wherein in S1, the number of times of extraction is 2, and the concentration is concentration under reduced pressure.

5. The method according to claim 2, wherein in S1, the drying is vacuum drying at 75 ℃.

6. The method according to claim 2, wherein, in S2, the number of times of extraction is 8.

7. The preparation method according to claim 2, wherein in S4, the gradient elution ratio of chloroform to methanol is 60:1, 40:1, 20:1, 10: 1.

8. The method for preparing capsinoid compound according to claim 1, comprising the steps of:

4-oxo-nonanoic acid is subjected to acyl chlorination and then reacts with homovanillic alcohol to obtain the capsaicine ester compound.

9. The use of the capsinoid of claim 1 as a standard for the determination of the capsinoid content in suberect spatholobus stem.

10. The use of the capsinoid compound of claim 1 and pharmaceutically acceptable salts thereof for the preparation of analgesic drugs.

Technical Field

The invention belongs to the field of natural phytochemistry, and particularly relates to a capsaicine ester compound obtained from caulis spatholobi, and a preparation method and application thereof.

Background

Compared with the capsaicin compounds, the capsaicin ester compounds have no pungent taste and cell activity of the capsaicin compounds, so the capsaicin ester compounds have better application value. Known researches show that the traditional Chinese medicine composition has the effects of enhancing the immune system, promoting fat metabolism, inhibiting obesity, relieving pain and the like. CN1791400A discloses that it has the effect of reducing the total serum cholesterol level and improving the arteriosclerosis index of a subject. Although the capsinoid compounds have received enough attention, the synthesis thereof has certain difficulties and the study on the activity thereof is still not thorough, and thus, the researches are still under intensive study.

Caulis Spatholobi is the dried rattan of Spatholobus Suffruticosa of Leguminosae, and the chemical components of caulis Spatholobi include flavonoids, lignans, terpenes, sterols, anthraquinones, phenolic acids and glycosides thereof. Despite the knowledge of a few large classes, researchers have been able to isolate new compounds in increasingly advanced extraction processes, some of which have been studied to find that they are more active in certain respects than compounds known to have similar structures, helping chemists to explore new pharmaceuticals, agricultural or other chemicals.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a capsaicine ester compound. The structure of the capsinoid compound is reported for the first time, and the capsinoid compound is derived from caulis spatholobi and can be used as a standard substance for identifying capsinoid substances in the caulis spatholobi. Surprisingly, the capsaicine ester compound also shows good analgesic performance and is expected to be used for preparing or developing new analgesic drugs.

The invention also aims to provide a preparation method of the capsaicine ester compound.

The invention also aims to provide application of the capsaicine ester compound.

The above object of the present invention is achieved by the following technical solutions:

a capsinoid compound and a pharmaceutically acceptable salt thereof, wherein the capsinoid compound has a structural formula shown as a formula (I):

the pharmaceutically acceptable salt of the capsaicine ester compound has a structural formula shown as a formula (II):

m is an alkali metal or an alkaline earth metal, and n is 1 or 2.

The capsinoid compound is found for the first time and can be named as 4-oxo-nonanoic acid homovanillic ester; it can be used as standard substance for identifying capsaicine ester in caulis Spatholobi.

In the present application, the alkali metal is selected from potassium, sodium, lithium; the alkaline earth metal is selected from calcium, magnesium and barium.

The preparation method of the capsaicine ester compound comprises the following steps:

s1, adding water into a caulis spatholobi certified medicinal material, performing reflux extraction, concentrating, and drying to obtain a caulis spatholobi dry extract;

s2, dissolving the caulis Spatholobi dry extract obtained in the step S1 with water, and extracting with ethyl acetate to obtain an ethyl acetate extract;

s3, chloroform is used: eluting S2 on a silica gel column by using a system with the methanol volume ratio of (70-90): 1, and obtaining an ethyl acetate extract to obtain a component Fr.1;

s4.Fr.1 is subjected to silica gel chromatography, chloroform-methanol is sequentially subjected to gradient elution by a ratio system of 60:1, (50-40): 1, (30-20): 1 and 10:1, and a component obtained by collecting the ratio of 10:1 is named as Fr.1-4;

s5.Fr.1-4 is detected by TLC and HPLC, RP-SP-HPLC is adopted to sequentially adopt acetonitrile with the volume ratio of 2:3, 11:9 and 4: 1: eluting in a water system, and collecting components obtained by eluting at a ratio of 4:1, namely Fr.1-4-3, and then adding acetonitrile at a volume ratio of (40-50) to (60-50): combining an aqueous solvent with RP-SP-HPLC to obtain the capsaicine ester compound.

In the invention, the caulis spatholobi certified drug is dried rattan of Spatholobus suberectus Dunn of leguminous plant.

Preferably, in S1, the mass ratio of the caulis spatholobi to water is 1: 5.

Preferably, in s1, the number of extractions is 2.

Preferably, in s1, the concentration is concentration under reduced pressure.

Preferably, in s1, the drying is vacuum drying at 75 ℃.

Preferably, in s2, the number of extractions is 8.

Preferably, in s3, the chloroform-methanol volume ratio is 80: 1.

Preferably, in S4, the gradient elution ratio of chloroform to methanol is 60:1, 40:1, 20; 1. 10; 1.

preferably, TLC tracing is performed while elution is performed by silica gel chromatography with chloroform-methanol at the ratio of 60:1, 40:1, 20:1, 10:1 in this order, and when the eluent obtained with the same ratio of eluent shows a change in composition, the eluent with the next ratio is changed.

Preferably, in s5. the acetonitrile: the volume ratio of the water solvent is 45: 55.

After the capsinoid compound is obtained, a corresponding salt can be obtained by reacting the capsinoid compound with an inorganic base formed from a corresponding alkali metal or alkaline earth metal.

The application also provides a synthetic method of the capsaicine ester compound, which comprises the following steps: 4-oxo-nonanoic acid is subjected to acyl chlorination and then reacts with homovanillic alcohol to obtain the capsaicine ester compound.

More specific reaction conditions are:

dissolving 4-oxo-nonanoic acid and pyridine in a solvent, slowly adding thionyl chloride at the temperature of-2 ℃, transferring to room temperature after dropwise addition, continuously stirring for 1h, heating for reflux, and carrying out TLC detection reaction until acyl chloride reaction is finished.

Preferably, the molar ratio of the 4-oxo-nonanoic acid to the thionyl chloride is 1: 1.5-2.5. More preferably 1: 2.

The solvent is preferably acetone.

The dropping speed is controlled to be over within 1 hour.

The capsinoid compound is applied to a standard substance for detecting the content of capsinoid in caulis spatholobi.

The analgesic effect of the capsaicinoid compound is unexpectedly found to be superior to that of high vanillic pelargonate ester through an analgesic experiment, so that the capsaicinoid compound is expected to be used for preparing or developing a new analgesic drug. Similarly, the pharmaceutically acceptable salt of the capsaicine ester compound is also expected to be used for preparing or developing new analgesic drugs.

Compared with the prior art, the invention has the following beneficial effects:

the invention discloses a novel capsaicine ester compound and pharmaceutically acceptable salt thereof, wherein the capsaicine ester compound is obtained by extracting and separating caulis spatholobi certified products and can be used as a standard substance for detecting the content of capsaicine substances in caulis spatholobi. The analgesic effect of the capsaicinoid compound is unexpectedly found to be superior to that of high vanillic pelargonate through an analgesic experiment, so that the capsaicinoid compound and the pharmaceutically acceptable salt thereof are expected to be used for preparing or developing new analgesic drugs.

Drawings

FIG. 1 is a mass spectrum of the capsaicinoid compound of the invention.

Detailed Description

The following examples are presented to further illustrate the present invention and should not be construed as limiting the invention. It is within the scope of the present invention to make simple modifications or alterations to the methods, procedures or conditions of the present invention without departing from the spirit and substance of the invention; unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.