Bacampicillin

Synthesis

Semi-synthetic antibiotic related to penicillin.

The relatively small chemical difference between ampicillin and benzylpenicillin not only allows for substantial oral activity but also results in a substantial broadening of antimicrobial spectrum so as to allow for use against many Gram-negative bacteria. Many devices have been employed in order to enhance still further the oral absorption of ampicillin. Bacampicillin is a prodrug of ampicillin designed for this purpose.

|inventor2-last=Sjöberg|inventor2-first=Berndt Olof Harald}}]] An azidopenicillin sodium salt (1) is reacted with mixed carbonate ester 2 (itself prepared from acetaldehyde and ethyl chloroformate) to give ester 3. Reduction of the azido linkage with hydrogen and a suitable catalyst produces bacampillin (4). Both enantiomers are active. The drug is rapidly absorbed from the gastrointestinal tract and is quickly cleaved by serum esterases to bioactive ampicillin, acetaldehyde, and ethanol.

References

References

1. (November 1975). "Bacampicillin: a new orally well-absorbed derivative of ampicillin". Antimicrobial Agents and Chemotherapy.
2. "Drugs@FDA: FDA-Approved Drugs, BACAMPICILLIN HYDROCHLORIDE".
3. (13 October 2015). "Organon USA Inc. et al.; Withdrawal of Approval of 67 New Drug Applications and 128 Abbreviated New Drug Applications".
4. "Penicilline und Verfahren zu deren Herstellung [Penicillin and method for manufacturing thereof]".
5. Ekstrom BA, Kovacs OK, and Sjoberg BO, (1973). Chem. Abstr., 80, 14921q(1974).
6. Ekstrom BA, Sjoberg BO, {{US patent. 3873521 and {{US patent. 3939270 (1975 and 1976 both to Astra).