Donald G. Walker

New cephalosporin acylating agents derived from syn-2- ( 2-aminothiazol-4 -yl) -2-methoxymininoacetic acid. Application to the synthesis of cefepime sulfate

Abstract Activation of the title acid 1 as acyl derivatives of 1-methyl-5-mercaptotetrazole ( 13 ) and 2-methyl-5-mercapto-1,3,4-thiadiazole ( 9 , 14 ) and subsequent acylation of penultimate 4 (X = Cl, I) gave good yields of cefepime sulfate 5 .

Synthesis of tritium-labeled azaline B acetate

Reaction of azaline B acetate (1) with freshly prepared trifluoroacetyl hypoiodite in trifluoroacetic acid - methylene chloride solution under anhydrous conditions produced a complex mixture of products from which compounds 2 and 3, resulting from iodination at the 1′-and 8′-positions of the Ac-D Nal1 residue, were isolated by preparative reversed-phase HPLC chromatography. Mass spectral analysis and 1H, 2D DQF-COSY and homonuclear 2D J-resolved NMR experiments confirmed these structures. Reductive tritiation of 2 over 10% Pd/C in EtOH - DMF (1:9, v/v) with 50 Ci T2 followed by chromatographic purification and salt exchange gave 37.5 mCi of tritiated azaline B acetate (4) having >98% chemical and radiochemical purities and a specific radioactivity of 11.2 Ci / mmol. A single peak at 7.59 ppm was observed in the proton decoupled tritium NMR spectrum.