Cephalothin: hydrolysis of the C-3'-acetoxy moiety of a 7-aminocephalosporanic acid; observation of both acyl-oxygen bond cleavage and reversible alkyl-oxygen bond cleavage.

The aqueous solution chemistry of the C-3'-acetoxy moiety of cephalothin sodium (1b) was examined with the use of isotopically labeled H2(18)O and [2-13C]acetate anion. The 18O incorporation studies indicate that the hydrolysis (at pH 4.7 +/- 0.1) of 1b to the deacetyl derivative of cephalothin (2b) proceeds via two pathways: alkyl-oxygen bond cleavage (55-63%) and acyl-oxygen bond cleavage accounting for the remainder. The incorporation of [2-13C]acetate into 1b suggests that the alkyl-oxygen cleavage pathway is a reversible reaction.