No abstract

A laboratory synthesis from the biosynthetic penicillins is described for cephalexin (7), an orally active deacetoxycephalosporin antibiotic. Penicillins V and G were converted to sulfoxide trichloroethyl esters 3a and 3b, respectively, by an esterification to compounds 2a and 2b followed by sulfoxidation. The sulfoxide esters 3a and 3b were rearranged thermally to their corresponding deacetoxycephalosporin esters 4a and 4b. Proof of structure for 4a and 4b was supplied by their independent syntheses from 7-aminodeacetoxycephalosporanic acid (9). N-Deacylation of 4a and 4b afforded a common amino ester, 7-aminodeacetoxycephalosporanic acid trichloroethyl ester (5d). Compound 5d was reacylated in mixed anhydride coupling reactions with A'-trichloroethyloxycarbonyl-D-a-phenylglycine and with A'-íerí-butoxycarbonyl-D-a-phenylglycine. The doubly protected cephalexin derivatives 6 and 12 were deblocked yielding cephalexin in good yield.

No abstract

The exo-methylene group in esters of 7-acylamido- and 7-amino-3-methylenecephams was ozonized to give 3-hydroxy-3-cephems. Conditions are described to effect a selective N-acylation of a 3-hydroxy-3-cephem nucleus ester. Vilsmeier reagents converted 7-acylamido-3-hydroxy compounds to 3-halo-3-cephem derivatives. Diazomethane converted the 3-hydroxy compounds to 3-methoxy-3-cephem derivatives. Removal of the ester-protecting group at the C4-carboxyl afforded a select group of cephalosporins with direct halo and methoxy substitution at C3. A number of these compounds are potent antibiotics.

Recently Schrauzer, et al., discovered that systems which consist of NaBH4, molybdate, and a thiol compound (cysteine, glutathione, or thioglycerol) (designated as Mo-SH systems) can reduce unsaturated