Cefroxadine
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = (6R,7R)-7-{[(2R)-2-amino-2-cyclohexa-1,4-dien-1-ylacetyl]amino}-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid
| image = Cefroxadine.svg
| tradename =
| Drugs.com = {{drugs.com|international|cefroxadine}}
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status = Rx-only
| routes_of_administration = Oral
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = ~1 hour
| excretion = Renal
| CAS_number = 51762-05-1
| ATC_prefix = J01
| ATC_suffix = DB11
| PubChem = 443991
| DrugBank =
| ChEMBL = 2104150
| ChemSpiderID = 4447587
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B908C4MV2R
| KEGG = D01528
| C=16 | H=19 | N=3 | O=5 | S=1
| smiles = O=C2N1/C(=C(/OC)CS[C@@H]1[C@@H]2NC(=O)[C@@H](C/3=C/C\C=C/C\3)N)C(=O)O
}}
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.{{cite journal |vauthors=Yasuda K, Kurashige S, Mitsuhashi S |title=Cefroxadine (CGP-9000), an orally active cephalosporin |journal=Antimicrobial Agents and Chemotherapy |volume=18 |issue=1 |pages=105–10 |date=July 1980 |doi=10.1128/AAC.18.1.105 |pmid=6998373 |pmc=283947}}
It is available in Italy.{{cite web |url=http://www.prontuario.it/ORASPOR/?f=xuiqqmolyaqmxu |author=[No authors listed] |title=Oraspor |work=Prontuario.it |publisher=Elsevier |language=it |access-date=2010-07-31}}
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).
File:Cefroxadine synthesis.svg|inventor1-last=Bickel|inventor1-first=Hans|inventor2-last=Scartazzini|inventor2-first=Riccardo}}R. Scartazzini, H. Bickel, {{US patent|4073902}} (1978 to Ciba-Geigy).R. B. Woodward and H. Bickel, {{US Patent|4147864}} (1979); Chem. Abstr., 91, 74633J (1979).]]{{clear left}}
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).