Preparation method of leonurine and aspirin conjugate

Abstract

The invention belongs to the field of medicinal chemistry, and relates to a synthesizing method of leonurine and aspirin conjugate. The method comprises the steps that syringic acid, S-methylisothiourea and aspirin serve as starting materials, reactions of acetylation, BOC protection, amidation, deacetylation and the like are conducted, and corresponding structure segments are obtained; dilauryl hydrogen phosphite, 4-dimethylaminopyridine and 4-toluenesulfonic acid are used together to serve as a condensation catalyst to connect the three segments, de-BOC protection is conducted on trifluoroacetic acid, and a target compound is obtained. The synthesizing method of the leonurine and aspirin conjugate is easy and convenient to operate, mild in condition, simple in post treatment and capable of increasing the yield of the intermediate leonurine product; the total yield of the prepared leonurine and aspirin conjugate is 25.27%, a pharmacological activity test is conducted, it is shown through the result that very good antioxidant and anti-apoptosis effects at a cellular level are achieved, and the effect on protecting myocardial cells is exact.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a conjugate of natural alkaloid leonurine and a non-steroidal anti-inflammatory drug aspirin, in particular to a preparation method of a conjugate of leonurine and its analogues and aspirin. Background technique [0002] In the prior art, Dongkai Leonurine is a specific alkaloid in Lamiaceae plant Leonurus, and relevant studies have shown that it has the ability to inhibit external Ca 2+ Influx and Ca 2+ Release and improve hemorheology, anti-oxidation, anti-apoptosis and other cardioprotective effects, and can promote the release of NO in vivo and in vitro. [0003] It is known that aspirin, also known as acetylsalicylic acid, is a common drug used clinically for analgesia and anti-inflammation. In recent years, studies have shown that aspirin can inhibit platelet aggregation, and has certain preventive and therapeutic effects on ischemic heart disease and angina pectoris. It ...

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Problems solved by technology

[0004] Studies have disclosed a variety of methods for the synthesis of motherwortine. Currently, the more commonly used synthetic routes include: using syringic acid and S-methylthiourea as starting materials, and preparing motherwort by acetylation, esterification, amidation, and hydrogenation reduction. Alkali, the disadvantage of its existence is: the yield of esterification reaction is low, the reaction catalyst is difficult to remove, and there is difficulty in purification; and temperature requirements are high, the acylating reagent used in the preparation process needs to be under anhydrous and oxygen-free conditions, and the operation has certain difficulties, etc.

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