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Neue Cephalosporine, die in 3-Stellung eine Fluormethylgruppe aufweisen (9, 17/Schema 1), wurden ausgehend von 2b unter Verwendung von 2-Chlor-1,1,2-trifluor-triathylamin als Fluorierungsmittel hergestellt. Mit Piperidin-schwefeltrifluorid erhielt man ferner aus 18 die 3-Difluormethyl-cephemverbindung 19 (Schema 2), die nach bekannten Methoden in antibakteriell wirksame Cephalosporine (20a, b) ubergefuhrt wurde. 3-Fluor-cephemderivate, z.B. 23b, liessen sich ausgehend von entsprechenden 3-Hydroxy-cephemverbindungen, mit diesem Reagens jedoch nur in sehr geringer Ausbeute herstellen.

New β-lactam antibiotics. Cephem derivatives with electron withdrawing substituents at position 3 Oxidation of the 3-formyl-2-cephem compound 1 according to Corey [6] gave 2-cephem-3-carboxylic esters 4a, b, c (Scheme 1), which proved to be useful intermediates for the synthesis of cephalosporins bearing in position 3 a methoxycarbonyl group (10a, b, c, d / Scheme 2) or a carboxy group (20, 25, 30/Schemes 3, 4). The 3-formyl-3-cephem compounds 31a, b could be transformed into cyano- (33a) or methoxyiminomethyl- (36a, c, d) cephems (Scheme 5), which represent further examples of cephalosporins with electron withdrawing groups in position 3.

7-Phenylacetamido-3-trifluoroacetoxymethyl-ceph-2-em-4-carboxlic acid (7), which is easily produced from the iso-cephalosporanic acid derivatives 4 or 6 by treatment with trifluoroacetic acid, reacts smoothly with ‘C-nucleophiles’ to give derivatives of type 5 (Schema 1 and 2). Compounds 5 are converted into microbiologically active cephalosporins of type 8 (Table) by previously described methods.