Novel 3-hydroxy, 3-methyl cephalosporins from the rearrangement of penicillin sulfoxides

✍ Scribed by Gerald E. Gutowski; Bennie J. Foster; Cecelia J. Daniels

• Publisher: Elsevier Science
• Year: 1971
• Tongue: French
• Weight: 190 KB
• Volume: 12
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)97198-9

✦ Synopsis

The acid catalyzed ring expansion (1) of penicillin sulfoxide esters, 1, to deacetoxy cephalosporins, 2, has assumed added importance due to the demonstrated oral effectiveness of the broad-spectrum antibiotic, cephalexin

(2). We now wish to report additional studies that further aid in elucidating the nature of this conversion, especially with respect to the crucial role of the acid catalyst in determining the products produced. CO,R CO,H -1 2 Cephalexin -During the course of the study of this rearrangement (3), variable amounts of a new %-lactam containing material could often be isolated in addition to 3-cephem ester 2. The characteristic AB pattern (Jgem = 14 Hz) of the C2 methylene protons and the usual H,double doublet (4) of this new compound suggested a cephalosporin derivative. However, the replacement of the vinyl methyl signal (normally found at 2.20 6 in 3-cephem's) with a singlet at higher field (1.26 6), together with infrared evidence for a saturated ester, and elemental analysis, led to the assignment of the 3-hydroxy, 3-methyl cepham structure, 3, for this novel moiety. Retention of H,-H, & stereochemistry in -2 was indicated by the coupling constant, J6_-7 = 4 HZ (4). Treatment of 2 with one equivalent of m-chloroperbenzoic acid affords the corresponding B-sulfoxide, whose configuration is confirmed by NMR hydrogen bonding studies

(5-7). The anisotropic effect of the %-sulfoxide (5) upon R., indicated that