Cephalosporin chemical reactivity

Conclusion

The inherent chemical reactivity of cephalosporins implies that the opening of the β-lactam ring by nucleophilic reagents generates an intermediate cephalosporoyl which is chemically unstable and that suffers multiple fragmentation reactions. Despite the structural similarities with penicillins, those cephalosporins that have a good R2 leaving group undergo the process of expulsion when they conjugate to carrier proteins by opening of the β-lactam ring. For these cephalosporins the unstable dihydrothiazine moiety is enough to undergo further degradation processes. As a result, conjugation of cephalosporins by the β-lactam ring leads to loss of the R2 side chain and to fractionation of the dihydrothiazine ring and this does not form part of the epitope presented in the hapten-carrier conjugate. Only the R1 side chain and a fragment of the β-lactam ring remain bound to the carrier protein, constituting the epitope resulting from these conjugates. The presence of an R2 side chain that may act as a good leaving group is closely related to enhanced reactivity of the β-lactam ring for nucleophilic attack. The effect of the R2 side chain on the conjugation of the carrier protein can be interpreted only from a kinetic perspective, such that an increase in the capacity of the R2 as a leaving group results in increased reactivity for the attack of nucleophiles to the β-lactam ring, increasing the facility and kinetics of the conjugation process.  Printer- Friendly Email ThisAcknowledgements

We thank Ian Johnston for the English version of the manuscript.Funding Information

Supported by grants from Ministerio de Sanidad (FIS PI02/0666, PI03/1165), Ministerio de Educacion y Ciencia (BQU 2001/3624) and Plan Andaluz de Investigacion Junda de AndaluciaAbbreviation Notes

RAST = radioallergosorbent test.Reprint Address

Correspondence to Ezequiel Perez-Inestrosa, Organic Chemistry, University of Malaga, 29071 Malaga, Spain E-mail: inestrosa@uma.es

Curr Opin Allergy Clin Immunol.  2005;5(4):323-330.  ©2005 Lippincott Williams & Wilkins
This is a part of article Cephalosporin chemical reactivity Taken from "Ceclor Cefaclor 250Mg" Information Blog