阅读说明：本技术 一类对香豆酸芳香衍生物及其制备方法和应用 (P-coumaric acid aromatic derivative and preparation method and application thereof ) 是由 李玉广 钦佩 杨雨顺 方莉 陈利丽 于 2019-10-03 设计创作，主要内容包括：本发明公开了一类对香豆酸芳香衍生物及其制备方法和应用。本发明的一类对香豆酸芳香衍生物,所述的一类对香豆酸芳香衍生物的结构式如式(I)所示：<Image he="467" wi="700" file="DDA0002224208610000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中,R选自：<Image he="91" wi="700" file="DDA0002224208610000012.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image><Image he="131" wi="700" file="DDA0002224208610000013.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明的化合物具有潜在的药物活性,其制备原料对香豆酸,可使用天然提取法获得,对于实现互花米草的资源化利用有积极的作用。(The invention discloses a p-coumaric acid aromatic derivative and a preparation method and application thereof. The structural formula of the p-coumaric acid aromatic derivative is shown as the formula (I): Wherein R is selected from: the compound has potential medicinal activity, and the preparation raw material of the compound is coumaric acid, can be obtained by a natural extraction method, and has a positive effect on realizing resource utilization of spartina alterniflora.)

1. a p-coumaric acid aromatic derivative is characterized in that the structural formula of the p-coumaric acid aromatic derivative is shown as a formula (I):

Wherein R is selected from:

2. A process for the preparation of aromatic derivatives of p-coumaric acid as claimed in claim 1, characterized in that it comprises the following steps:

Dissolving p-coumaric acid in a mixed solution of dichloromethane and N, N-dimethylformamide, adding a plurality of aromatic sulfonyl chlorides, stirring for 30-60min under an ice bath condition, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine, moving to room temperature, stirring for 5-8h, carrying out thin-layer chromatography tracking reaction, filtering a precipitate after the reaction is finished, extracting a filtrate by using an extracting agent, washing by using a saturated sodium chloride solution, drying by using saturated sodium sulfate, distilling under reduced pressure to remove an organic solvent, and recrystallizing by using a mixed solvent of N, N-dimethylformamide and ethanol to obtain the p-coumaric acid aromatic derivative.

3. the method for preparing aromatic derivatives of p-coumaric acid according to claim 2, characterized in that: the mol volume ratio of p-coumaric acid to dichloromethane is 1 mmol: 10mL, wherein the volume ratio of the dichloromethane to the N, N-dimethylformamide is 10: 1.

4. The method for preparing aromatic derivatives of p-coumaric acid according to claim 2, characterized in that: the molar ratio of the p-coumaric acid to the aryl sulfonyl chloride to the dicyclohexylcarbodiimide to the 4-dimethylaminopyridine is 1: 1: 1.5: 0.5.

5. The method for preparing aromatic derivatives of p-coumaric acid according to claim 2, characterized in that: the volume ratio of the N, N-dimethylformamide to the ethanol is 1: 9.

6. The method for preparing aromatic derivatives of p-coumaric acid according to claim 2, characterized in that: the extractant is ethyl acetate or dichloromethane.

7. The method for preparing aromatic derivatives of p-coumaric acid according to claim 2, characterized in that: the saturated sodium chloride solution is washed for more than 3 times.

8. use of the aromatic p-coumaric acid derivative according to any one of claims 1 to 7 for the resource utilization of spartina alterniflora.

9. use of an aromatic p-coumaric acid derivative according to any one of claims 1 to 7 for the preparation of a medicament.

Technical Field

The invention relates to the technical field of medicinal chemistry, in particular to aromatic derivatives of p-coumaric acid and a preparation method and application thereof.

Background

Hydroxycinnamic acid compounds have wide application in pharmaceutical chemistry, wherein p-coumaric acid is a reported important prodrug molecule and has activities of resisting oxidation, resisting bacteria, treating cardiovascular diseases and the like. The development of coumaric acid drugs has important significance for treating hyperuricemia and gout. In the production method of coumaric acid, the chemical synthesis method is easy to cause pollution to the ecological environment, and the biotransformation method is limited by the variety of fermentation raw materials and cannot be used as a stable production source, so the natural extraction method is the technical means which most accords with the concepts of environmental protection and quality control. The drug precursor molecules are modified by using sulfonyl chloride with reference to drugs such as busulfan, sulfonate mucopolysaccharide and the like, so that the active improvement effect can be generally obtained, and the method has better feasibility for further development of hydroxyl-containing drugs.

The spartina alterniflora enters the sight of the research workers in the field medical department by investigating the plants capable of serving as the source of the coumaric acid and comprehensively considering the potential economic value and ecological significance. The grass is a long-stalk herbaceous plant, is perennial in gramineae, is successfully introduced into China in a plurality of provinces in coastal areas of China in more than ten years after the introduction of professor Zhongchong letter of Nanjing university in 1979, makes great contribution to bank protection, but is widely considered as a species threatening the biodiversity of the coastal areas due to the lack of ecological competition and needs to be subjected to prevention and control treatment. Taking scientific researchers in halophyte laboratories of Nanjing university as a representative, the management idea of spartina alterniflora has gradually changed from traditional high-cost schemes such as harvesting control and the like to the realization of resource utilization, and flavone, polyphenol and other raw materials are obtained by a natural extraction method, and potential medicines are further developed. At present, the edibility of the spartina alterniflora extract (new resource food of Ministry of health, Weixin food Standard 94 No. 06) is solved internationally, and great economic benefit can be generated while ecological environment restoration is realized inevitably in further drug development.

at present, a p-coumaric acid aromatic derivative for realizing the resource utilization of the spartina anglica and a preparation method and application thereof are lacked.

disclosure of Invention

The invention aims to provide p-coumaric acid aromatic derivatives for realizing the resource utilization of spartina anglica, and a preparation method and application thereof.

The purpose of the invention is realized by the following technical scheme: the structural formula of the p-coumaric acid aromatic derivative is shown as the formula (I):

Wherein R is selected from:

the invention relates to a synthetic process of p-coumaric acid aromatic derivatives, which has the following general formula:

Wherein R is selected from:

The preparation method of the p-coumaric acid aromatic derivative comprises the following steps:

Dissolving p-coumaric acid in a mixed solution of dichloromethane and N, N-dimethylformamide, adding a plurality of aromatic sulfonyl chlorides, stirring for 30-60min under an ice bath condition, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine, moving to room temperature, stirring for 5-8h, carrying out thin-layer chromatography tracking reaction, filtering a precipitate after the reaction is finished, extracting a filtrate by using an extracting agent, washing by using a saturated sodium chloride solution, drying by using saturated sodium sulfate, distilling under reduced pressure to remove an organic solvent, and recrystallizing by using a mixed solvent of N, N-dimethylformamide and ethanol to obtain the p-coumaric acid aromatic derivative.

further, the molar volume ratio of p-coumaric acid to dichloromethane is 1 mmol: 10mL, wherein the volume ratio of the dichloromethane to the N, N-dimethylformamide is 10: 1.

further, the molar ratio of the p-coumaric acid to the aryl sulfonyl chloride to the dicyclohexylcarbodiimide to the 4-dimethylaminopyridine is 1: 1: 1.5: 0.5.

Furthermore, the volume ratio of the N, N-dimethylformamide to the ethanol is 1: 9.

further, the extracting agent is ethyl acetate or dichloromethane.

Further, the saturated sodium chloride solution was washed 3 times or more.

The application of the aromatic derivatives of p-coumaric acid in the resource utilization of spartina alterniflora is disclosed.

The invention relates to application of aromatic derivatives of p-coumaric acid in preparing medicaments.

Has the advantages that: the preparation raw material p-coumaric acid of the p-coumaric acid aromatic derivative can be obtained by using spartina alterniflora as a raw material and using a natural extraction method, and is favorable for promoting the realization of resource utilization of the spartina alterniflora. The obtained aromatic derivatives of p-coumaric acid have potential pharmaceutical activity and can be applied to further drug development.

Detailed Description

The present invention is further illustrated in detail by the following examples, but it should be noted that the scope of the present invention is not limited by these examples at all.