Synthesis method of mannosidase inhibitor Kifunensine

Abstract

The invention provides a synthesis method of mannosidase inhibitor Kifunensine. L-gulonic acid-gamma-lactone, which is cheap and easily available, is taken as an initial raw material to efficiently obtain the Kifunensine through multi-step chemical conversion, the overall yield of the reaction is high, reagents used in the process are cheap and easily available, and multiple steps in the synthesis process can be fed by a one-pot method, so that the operation is simple and convenient, and the method has a better industrial prospect.

Description

technical field [0001] The invention belongs to the technical field of compound synthesis, and in particular relates to a synthesis method of Kifunensine, a mannosidase inhibitor. Background technique [0002] Kifunensine (structural formula shown below) is an alkaloid isolated from the actinomycetes called Kitasatosporia kifunense. It is a neutral, stable compound. Kifunensine is a potent inhibitor of mannosidase I, compared to other mannosidase inhibitors such as deoxymannan, it rapidly penetrates into cells where it prevents endoplasmic reticulum mannosidase I (ERM) repairs mannose residues in precursor glycoproteins, thereby inhibiting glycosylation, while it has no inhibitory effect on mannosidase II and has a weak inhibitory effect on aryl mannosidase. Therefore, when incorporated into the cell culture medium, Kifunensine has no effect on cell growth or glycoprotein production, and can greatly improve the quality and expression of the prepared glycoprotein. Based on...

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Problems solved by technology

[0004] At present, there are fewer methods for synthesizing Kifunensine. People such as P.A.Benjes have reported a kind of synthetic route (US20040063973A1) with N-acetyl-D-mannosamine as the starting material. The method has 8 steps of reaction conversion, and the total The yield is relatively high, but the reproducibility of this route is poor, especially in the step of oxidative ring closure. During amplification, the yield is often greatly reduced, and a large amount of impurities will be produced, which is very unfavorable for purification. Sometimes even the product cannot be obtained. In addition, the starting material of this route is relatively expensive, and the market price of N-acetyl-D-mannosamine is very expensive, which is not conducive to mass production

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