Pyridine Cephaloridine

Thienylacetarnidocephalosporanic acid (7.0 g) was suspended in water (60 ml) and stirred with pyridine (7 ml) until the acid dissolved. The resulting solution (pH 5.9) was kept at 35°C for 3 days, then filtered and extracted with methylene chloride (4 x 60 ml). The methylene chloride extract was back-axtracted with a little water and the total aqueous solutions were then percolated through a column of Dowex 1x8 resin, (100 to 200 mesh, 150 g) in the acetate form at pH 4.3. The column was washed with water until the optical rotation of the eluate fell to zero and the eluate (500 ml) was freeze-dried. The residual white solid was dissolved in the minimum volume of methanol and after a few minutes the pyridine derivative crystallized this is the cephaloridine product. 

The second necessary fragment, 7-amino-3-(l-pyridinomethyl)cef-3-en-carbonic acid (32.1.2.80), is synthesized from cefalosporidin (32.1.2.79), a cephalosporin antibiotic that is used independently in medicine and which is synthesized in the form of an internal salt by reacting cefalotin (32.1.2.1) with pyridine to replace the acetoxyl group with a pyridine group. Initially treating cephaloridin with trimethylchlorosilane in the presence of dimethylaniline and then with phosphorous pentachloride, followed by a reaction with 1,... 

Also, there is some correlation between accumulation and nephrotoxicity. For example, neonatal rabbits lacking a developed OAT 1 are less susceptible to the nephrotoxic effects of the drug. Similar drugs, such as cephalothin (Fig. 7.34), lacking the pyridine ring and, so, not cationic, are not nephrotoxic and do not accumulate (Table 7.7). This accumulation of cephaloridine is presumed to be due to the cationic group reducing efflux. 

Farad WS, Pratt RF. Elimination of a good leaving group from the 3 -position of a cephalosporin need not be concerted with P-lactam ring opening TEM-2 P-lactamase-catalysed hydrolysis of pyridine-2-azo-4 -(N, N -dimethylanUine) cephalosporin (PADAC) and of cephaloridine. 1 Am Chem Soc. 1984 106 1489-90. 

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