Intermediate of fondaparinux sodium and preparation method for intermediate and fondaparinux sodium

Abstract

The invention discloses an intermediate of fondaparinux sodium and a preparation method for the intermediate and the fondaparinux sodium. The preparation method is as follows: a protective pentasaccharide compound III is subjected to esterolysis reaction at presence of sodium hydroxide, the hydrolyzed compound is sulfated to obtain a compound IV, an intermediate compound I reacts with SO3 in pyridine at the temperature of 50 DEG C for 18 h and sulfated to obtain a compound II, the compound II is subjected to catalytic hydrogenation in methyl alcohol and water with palladium hydroxide or a palladium carbon catalyst to enable the compound II to get rid of all R groups to obtain the fondaparinux sodium. According to the invention, the reactions are high in selectivity and specificity and the productive rate of each reaction can reach about 90%; the obtained crude product of the intermediate is relatively high in purity, easy to supervise and trace, and relatively high in productive rate without need for purification; the operation is simple and the reproducibility is good; final products are obtained through the catalytic hydrogenation with benzyl groups and protecting groups removed, the final products are high in purity and suitable for large-scale industrial production, the production cost is greatly reduced, and the products are competitive in markets.

Description

technical field [0001] The invention relates to a preparation method for converting fully protected pentasaccharide into fondaparinux sodium. Background technique [0002] Heparin, a polymer of sulfonated amino sugars, has been clinically used in the treatment of thrombus and embolism since 1935. The combination of heparin and antithrombin (ATⅢ) causes the conformational change of antithrombin, activates antithrombin, reduces the activation of thrombin and protease in the blood circulation, especially reduces the activity of factor Xa. [0003] Factor Xa activity decreases more than 1,000-fold faster due to the presence of heparin. Heparin forms complexes with antithrombin and thrombin, thereby inhibiting the activity of factor Xa. Therefore, the size of the heparin molecule determines its ability to inhibit the activity of factor Xa. The pentose sugar sequence in heparin binds to and activates antithrombin. Compared with heparin molecules, low-molecular-weight heparin c...

AI Technical Summary

Problems solved by technology

[0012] The intermediates of all reactions in the above methods are unstable, the reactions are not easy to track, the product separation is difficult, the yield is unstable, and the reaction reproducibility is not good, thus bringing greater difficulties to the separation and purification of the final product, and the first The reactions in step 3 and step 4 are not specific reactions, the monitoring and separation of these reactions are problematic, and the yield will not be high

Images