Cefaclor and Related Derivatives

In the search for alternative routes to cephalexin the discovery of a practical preparation of 3-methylenecephams was truly serendipitous. 

A key step in this preparative scheme was the low-temperature ozonolysis of 3-methylenecephams (Chauvette and Pennington, 1974, 1975). Initial oxidation studies had shown that the ozonolysis of 7-acylamino- 

N-Acylation of the 3-hydroxy-3-cephem nucleus ester (107) was best accomplished in aqueous media. For example, an acid chloride in dry solvent added dropwise to 107 in an aqueous tetrahydrofuran solution containing sodium bisulfite gave good yields of 7-acylamino-3-hydroxy-3-cephem esters (108). Because of the zwitterionic character of 107, its 

The structure of this product was later confirmed when it was alternatively prepared from authentic 3-chloro-3-cephem nucleus ester (116) 

A more expanded list of MICs (Table III) affirms the superiority of the in vitro antibacterial spectrum of cefaclor over that of cephalexin (Preston and Wick, 1974). The in vitro spectra of cefaclor and its p-hydroxy derivative (123n) appear in Table IV. The data are comparable for the two antibiotics (D. A. Preston, unpublished data). Oral therapy of mice experimentally infected with Streptococcus pyogenes, S. pneu-  

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