Study On The Synthetic Process Of The Cefprozil

Cephalosporin antibiotics have been widely used in clinical treatment of diseases which were caused by pathogenic bacteria.and they have been developed into the fourth-generation.Cefprozil was an orally effective cephalosporin antibiotic having a broad spectrum of antibacterial activity against both gram-positive and gram-negative organisms.The synthetic processes of 7-amino-3-(propen-l-yl)-3-cep-hem-4-carboxyJic acid(7-APCA) and cefprozil were researched. After investigation of a series of synthetic routes, the best route has been determined which was easy to operate on industrial scale.7-APCA was an important synthetic intermediate in the preparation of cefprozil. 4-methoxybenzy17-phenylacetamido-3-(propen-l-yl)-3-cephem-4-carboxylate(GPRE) was synthesized from 4-methoxybnzyl7-phenylacetamido-3-chloromethyl-3-cep-hem-4-carbo-xylate(GCLE) by the Wittig reaction. Then GPRE was hydrolyzed by aluminium choride to remove the carboxyl protecting group to get 7-phenylacetami-do-3-(propen-l-yl)-3-ce-phem-4-carboxylic acid.7-phenylacetamido-3-(propen-l-yl)-3-cephem-4-carbox-ylic acid was enzymatic hydrolyzed to remove the amino protecting group, and 7-APCA was obtained. The total yield was 65.36% and the purity of the product was higher than 93%.7-APCA was suspended in an appropriate solvent and an amidine was added. 7-APCA was in the form of a salt with a guanidine which guanidine was in the form of a free base, the solution may be obtained. In another aspect, the formation of the mixed carboxylic acid anhydride was present under the reaction of Dane salts with the acylating agent. Formation of cefprozil in the form of a DMF-solvate under the reaction of 7-APCA-amidine and the mixed carboxylic acid anhydride. And then, the cefprozil in the form of a DMF-solvate was converted into cefprozil in the form of a monohydrate by heating a solution or suspension in water at elevated temperates. The total yield was 63%.The chemical structures of cefprozil had been characterized by means of IR and 'H-NMR. The proauct quality accords with the standard of Chinese pharmacopoeia.