Synthesis and Properties of Disodium Tetraethyleneglycol-bis-(α-carboxybenzylpenicillin)

Abstract

Disodium tetraethyleneglycol-bis-(α-carboxybenzylpenicillin) (TEG-carbenicillin), a tetraethyleneglycol (TEG) diester of carbenicillin, was synthesized to develop a carbenicillin prodrug with enhanced acid stability for oral administration. Antimicrobial activities of TEG-carbenicillin tested against gram-negative Escherichia coli (TG-1) and gram-positive Staphylococcus aureus (ATCC-12228) and Bacillus subtilis (NA-1) were comparable to that of carbenicillin. Stability of the β-lactam ring of TEG-carbenicillin was determined by iodometry at pH 6.8, pH 4.5, and pH 2.0 at varied time intervals and was compared to that of carbenicillin. In 26 hr, both of the compounds were stable at pH 6. 8. At pH 4.5, about 41% of the carbenicillin was decomposed, while TEG-carbenicillin was not appreciably decomposed. At pH 2.0, carbenicillin was decomposed about 61% after 6 hr, while TEG-carbenicillin was decomposed about 21% during the same period.

Key Words:

• Carbenicillin
• Disodium tetraethyleneglycol-bis-(α-carboxybenzylpenicillin)
• Tetraethyleneglycol