Mitsuo Numata

NEW CEPHALOSPORINS WITH 7-ACYL GROUPS DERIVED FROM β-KETOACIDS

The synthesis and antimicrobial profile of a series of 7-(beta-ketoacylamino)cephalosporins (1) bearing an acetoxymethyl or a heterocyclichiomethyl group at the 3-position are described. Of this series, 3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-7-(3-oxobutyrylamino)ceph-3-em-4-carboxylic acid (11) showed moderate antibacterial activities in in vitro and in vivo tests.

The metabolism of the octamethylene-1,8-dithiol moiety of BIS(O-acetylthiamine)octamethylene-1,8-disulfide in rat and man☆

Abstract Metabolic fate and urinary metabolites of the octamethylene-1,8-dithiol moiety of bis ( O -acetylthiamine)-octamethylene-1,8-disulfide (BTOD) have been studied in rat and man. Following the i.v. administration of 35 S-labeled BTOD, the rat excreted about 75 per cent of the administered radioactivity in urine and 4 per cent in feces within 2 days. Upon the oral or i.p. administration, the rat excreted 44–50 per cent in urine and 35–45 per cent in feces. No significant radioactivity was found in the respiratory gas in either cases. Three metabolites were isolated by silicic acid chromatography from urine obtained after oral administration of the compound. The spectrometric data (infrared and nuclear magnetic resonance) demonstrated that their chemical structures were 1,8- bis (methylsulfinyl)octane, 1-methylsulfinyl-8-methylsulfonyloctane and 1,8- bis (methylsulfonyl)octane, respectively. The identity of these-metabolites was conclusively established by comparison studies with authentic compounds which were chemically synthesized. These three metabolites were also recognized in the human urine after oral administration of nonlabeled BTOD. The excretion pattern of the radioactivity following the oral administration of 35 S-labeled octamethylene-1,8-dithiol was very similar to that obtained with BTOD. Identical metabolites were characterized in urine after i.p. administration of the dithiol. The present studies show that the sulfur in the compounds is metabolized solely by the methylsulfonyl pathway and conversion to inorganic sulfate does not occur in any appreciable amount.