Solutions For An Introduction to Medicinal Chemistry Chapter 19 Problem 8Q

The activities such as β-lactamase activity and acid tolerance are observed in it. The drug can be taken orally due to these properties. It is found effective in the people who are sensitive towards penicillin. Cefoxitin structure has modifications imparting properties better than the native cephalosporin.

Figure: Structure of Cefoxitin

In Cefoxitin, the methyl group of an ester is replaced by the NH₂ (amine) group. This functional group is more stable than the ester group and it imparts stability to the new structure. The NH₂ has same valence and size, thus does not show any steric effect, but has different electronic properties.

Figure: Native structure of Cephalosporin

The NH₂ group can add a lone pair of electrons to the structure, thus imparts structural stability, which is not seen in the case of the methyl group attached to the native structure of cephalosporin.

The analogue of Cefoxitin might show properties similar to that of the native cephalosporin. In the case of Cefoxitin analogue, the methyl group is replaced by trifluoromethyl. In trifluoromethyl, the methyl group has fluorine instead of hydrogen.

The valence of new analogue is found similar to the native cephalosporin, but trifluoromethyl has a bulky structure as compared to the methyl group. This may show steric effect leading to hindrance during attachment to the active site. Hence, the new analogue would be more unstable than the Cefoxitin.

Figure: Structure of analogue of Cefoxitin