Novel route for clindamycin phosphate compounds

Abstract

The invention provides a novel route for clindamycin phosphate compounds. In particular, clindamycin serving as an initial reaction raw material undergoes hydroxyl protection, phosphorylation and hydrolysis reaction to obtain the clindamycin phosphate compounds. In the new route, a specific catalyst is used and phosphorus oxychloride is used as a phosphorylating agent, so that compared with the prior art, the new route has the advantages of greatly lowering consumption of phosphorus oxychloride, lowering production cost and being more suitable for industrialization.

Description

technical field [0001] The invention relates to a new route of clindamycin phosphate compound, which belongs to the field of drug synthesis. Background technique [0002] Clindarnycin, whose chemical name is 7(s)-chloro-7-deoxylincomycin, has the same antibacterial mechanism and antibacterial spectrum as lincomycin, but the antibacterial effect can be increased by 4-8 times. Its outstanding effect on Gram-positive bacteria, especially anaerobic bacteria, is a major feature of this product. Clindamycin is well absorbed after oral administration in the form of hydrochloride, and the food in the stomach and duodenum does not affect its absorption; the plasma half-life is 2-5h, and most of it has been metabolized in the body, only about 10% is excreted from the urine Excretion; the plasma half-life is slightly prolonged in patients with renal insufficiency, but there is no need to adjust the dose, and no allergy test is required before use. It is effective for bacteria resistan...

AI Technical Summary

Problems solved by technology

[0006] In the synthesis process of clindamycin phosphate reported in the literature, the 3 and 4 hydroxyl groups are usually protected by the method of forming arylene and propylene groups. However, because the arylene group is difficult to remove, it is not used in production Propylene protection has the advantages of easy operation, mild deprotection conditions, and low cost, and is widely used in production. However, because the latter is a reversible reaction, the reaction is incomplete and the related substances in the final product are too high and do not meet the Pharmacopoeia Standard requirements. At the same time, the phosphorylation of clindamycin after protection must be carried out in a large amount of anhydrous pyridine solvent, because pyridine is expensive, highly toxic, and difficult to recover and purify, resulting in high production costs and lack of market competitiveness. With the intensification of competition in the raw material drug market and the improvement of quality standards, it is of great practical significance to carry out research on the new synthesis process of clindamycin phosphate to improve product quality, ensure drug safety, reduce production costs, and participate in international market competition.

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