Method for preparing 3-deacetyl-7-aminocephalosporanic acid

Abstract

The invention discloses a method for preparing 3-deacetyl-7-aminocephalosporanic acid, which comprises the following steps: catalyzing extract of cephalosporin C serving as a raw material by D-amino-acid oxidase to prepare solution of glutaryl-7-ACA; catalyzing the solution of glutaryl-7-ACA by glutaryl-7-ACA acylase and cephalosporin esterase to prepare solution of 3- deacetyl-7-aminocephalosporanic acid; and performing acidification crystallization, washing and drying to obtain solid 3-deacetyl-7-aminocephalosporanic acid. The method for preparing the3-deacetyl-7-aminocephalosporanic acid only needs two steps of normal temperature reaction and one-time crystallization process and has short process route; solvents are not used basically; the molar yield from the extract of the cephalosporin C to the 3-deacetyl-7-aminocephalosporanic acid can reach 71.5 percent; and the yield of the product is high. In addition, compared with the prior art, the method has much lower energy consumption, power cost, labor cost and environmental cost.

Description

technical field [0001] The invention relates to a preparation method of pharmaceutical raw materials, in particular to a preparation method of 3-deacetyl-7-aminocephalosporanic acid. Background technique [0002] 3-Deacetyl-7-aminocephalosporanic acid is referred to as D-7-ACA. Because the 7-position amino group and 3-position hydroxyl group of D-7-ACA are relatively active, different side chains can be introduced to synthesize a series of cephalosporin antibiotics according to the needs. , such as cefuroxime, cefpirome, cefcapene, cefixime, cefdinir, ceftazidime, etc. Cephalosporin antibiotics have the characteristics of broad-spectrum antibacterial properties and small toxic and side effects. They are currently the most widely used antibiotics in clinical practice. The demand for 7-ACA is also increasing. [0003] The method for preparing D-7-ACA mainly contains two kinds at present: a. Cephalosporin C sodium salt (or zinc salt) obtains 7-ACA (7-aminocephalosporin) by es...

AI Technical Summary

Problems solved by technology

The above-mentioned existing D-7-ACA preparation method: the process route is long and must go through three crystallization processes of cephalosporin C sodium salt (or zinc salt), 7-ACA, and D-7-ACA, because the crystallization process yield loss many, resulting in a low yield, the calculation method a and b are respectively 65.2% and 67.8% from the molar yield of cephalosporin C extract to D-7-ACA, in addition, method a adopts chemical cracking, and its process consumes a lot of Cryogenics and solvents, and methylene chloride, aniline, and chlorosilane used in the reaction materials are all toxic and harmful pollutants, making the production of D-7-ACA bear heavy energy consumption costs and pollution control costs Method b adopts enzymatic method to prepare 7-ACA, and then obtains D-7-ACA by chemical or enzymatic cleavage, because the crystallized product is sticky, difficult to centrifuge and dry when enzymatic cleavage of 7-ACA crystallization, Need to add solvent to assist crystallization, and use a lot of separation equipment, resulting in increased energy consumption and labor costs