Synthesis method of pidotimod

Abstract

The invention provides a synthesis method of pidotimod disclosed as Formula (1). The synthesis method comprises the following steps: (1) carrying out condensation reaction on thioproline and cyprolidol under the actions of a catalyst and a condensation reaction solvent to obtain an intermediate I; (2) carrying out condensation reaction on the intermediate I and pyroglutamic acid under the actions of a catalyst and a condensation reaction solvent to obtain an intermediate II; and (3) dropwisely adding an acidic material into the intermediate II, and carrying out degreasing reaction in a degreasing reaction solvent. The synthesis method avoids using thionyl chloride, pentachlorophenol and other toxic reagents, and thus, has favorable environment friendliness. The method does not need strong alkali high-temperature esterolysis, so the synthesis process is milder. The intermediate I and intermediate II can absorb ultraviolet light, so that the whole synthesis progress can be monitored conveniently. In addition, the optical purity of the pidotimod prepared by the synthesis method is higher.

Description

Technical field [0001] The invention relates to the technical field of biomedicine, in particular to a method for synthesizing pidotimod. Background technique [0002] Pidomod (pidotimod), whose chemical name is (R)-3-[(S)-(5-chloro-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, was developed in the 1980s The immunomodulator developed by Poli industria chemical SPA, Italy, was approved to be marketed in 1993. It has antiviral, anti-irritation, anti-infection, and anti-oxidant activities. It is mainly used to prevent and treat children with recurrent respiratory infections, urinary system infections, and allergies. Rhinitis and asthma, treatment and prevention of acute chronic bronchitis, upper respiratory tract infections, and can also be used for a variety of viral infections, malignant tumors and other chronic diseases that cause the body's immune function to become low. [0003] Currently, there are two main synthetic routes for pidotimod. [0004] Synthetic route one:...

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Problems solved by technology

[0013] The object of the present invention is to disclose a kind of synthetic method of pidotimod, in order to overcome the need to use toxic reagents such as thionyl chloride, pentachlorophenol in the existing synthetic route, and need high-temperature esterolysis of strong alkali in the prior art, The synthesis process is not gentle, it is not easy to monitor defects such as the progress of the synthesis, and improve the optical purity of the product

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