Synthesis method of meropenem

Abstract

The invention relates to a synthesis method of meropenem, which particularly comprises the following reaction routes: dissolving a compound of the formula (IV) and a compound of the formula (V) into an organic solvent, and then performing a condensation reaction under the action of condensing agent to obtain a compound of the formula (II); dissolving the compound of the formula (II) and a compound of the formula (VI) into methyl benzene, acetic ether or tetrahydrofuran, and then performing a reaction under the action of alkali to generate a compound of the formula (III); dissolving the compound of the formula (III) into cyclohexane, n-octane, the methyl benzene or dimethyl benzene, and then performing a Wittig cyclization reaction under the action of an organic phosphor agent to obtain a compound of the formula (VII); dissolving the compound of the formula (VIII) into a solvent consisting of one of or a plurality of methanol, ethanol, tert-butyl alcohol, isobutanol, isopropanol, the tetrahydrofuran, dioxane, acetone, dichloromethane, chloroform and water, and performing hydrogenation under the action of a palladium catalyst to remove allyl and obtain a target product (I). The synthesis method of the meropenem has the advantages of high yield, mild reaction condition, little environmental pollution, and brief routes.

Description

technical field The invention relates to a β-methyl carbapenem antibiotic, in particular to a preparation method of meropenem. Background technique Carbapenem (Carbapenem) is a new type of β-lactam antibiotic, known for its broad antibacterial spectrum and strong antibacterial effect, such as Meropenem (Meropenem), imipenem (Imipenem) And Biapenem (Biapenem), etc., play an important role in curing severe infections. As for the synthesis method of penems, most of the previous studies were to synthesize the corresponding penem side chain compound and the mother core MAP respectively, and then condense the two to remove the protecting group to obtain the penem product. For example, USP4933333 uses 4-acetoxyazetidinone (4AA) as the starting material to obtain the mother core MAP after several steps of reaction. Meropenem is obtained by condensation and deprotection of the mother nucleus and the side chain. However, this method is cumbersome, the synthesis steps are long, a...

AI Technical Summary

Problems solved by technology

This method has a short route, simple operation, and simple and easy-to-get raw materials, but there are also some areas that need improvement.

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