Cefroxadine (INN, trade names Oraspor and Cefthan-DS) is a cephalosporin antibiotic. It is structurally related to cefalexin, and both drugs share a similar spectrum of activity.[1]

It is available in Italy.[2]

Synthesis

Cefroxadine can be prepared by several routes, including one in which the enol is methylated with diazomethane as a key step. A rather more involved route starts with comparatively readily available phenoxymethylpenicillin sulfoxide benzhydryl ester (1).

Synthesis of cefroxadine[3][4][5]

This undergoes fragmentation when treated with benzothiazole-2-thiol to give 2. Ozonolysis (reductive work-up) cleaves the olefinic linkage and the unsymmetrical disulfide moiety is converted to a tosyl thioester (3). The enol moiety is methylated with diazomethane, the six-membered ring is closed by reaction with 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU), and the ester protection is removed with trifluoroacetic acid to give 4. The amide side chain is removed by the usual PCl5/dimethylaniline sequence followed by reamidation with the appropriate acid chloride to give cefroxadine (5).

See also

References

  1. ^ Yasuda K, Kurashige S, Mitsuhashi S (July 1980). "Cefroxadine (CGP-9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy. 18 (1): 105–10. doi:10.1128/AAC.18.1.105. PMC 283947. PMID 6998373.
  2. ^ [No authors listed]. "Oraspor". Prontuario.it (in Italian). Elsevier. Retrieved 2010-07-31.
  3. ^ DE 2331133, Bickel, Hans & Scartazzini, Riccardo, "Enolderivate [Enol derivatives]", published 1974-01-17, assigned to Ciba-Geigy AG 
  4. ^ R. Scartazzini, H. Bickel, U.S. patent 4,073,902 (1978 to Ciba-Geigy).
  5. ^ R. B. Woodward and H. Bickel, U.S. patent 4,147,864 (1979); Chem. Abstr., 91, 74633J (1979).
Allikas: https://en.wikipedia.org/wiki/Cefroxadine
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