Epimerization of erythromycin derivatives.

Dirithromycin (3) isomerizes upon dissolution in different solvents. From X-ray analysis of V-T 108, an analogue of dirithromycin, and comparative 1H and 13C NMR, and MS data, the isomer of dirithromycin was confirmed to be the C-16-(S)-epimer. The ratio of the two epimers at equilibrium conditions was approximately 8:2 (R/S) in methanol at room temperature.

Synthesis and antimicrobial activity of 7 alpha-methoxypyrimidinyl-ureidocephalosporins.

The synthesis of a series of 7 alpha-methoxy-7-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(4-hydroxyphenyl) acetamido]-3-cephem-4-carboxylates 2 is described. 7-[(R)-2-[3-[2-(p-Aminosulfonyl)-anilino-4-hydroxy-5-pyrimidinyl]ureido- 2-(4-hydroxyphenyl)acetamido]-7 alpha-methoxy-3-[(1-methyl-1H-tetrazol-5 -yl)thio]methyl-3-cephem-4-carboxylic acid, sodium salt (2k, UG-FA 132), has exhibited a broad range of antimicrobial activity. UG-FA 132 is highly active against Gram-positive and Gram-negative organisms, including Pseudomonas and lactamase producers, and shows potent activity against anaerobes.

Synthesis and antimicrobial activity of pyrimidinylureidocephalosporins.

The synthesis of a series of 7R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(aryl)acetamido]-3-cephem-4- carboxylates is described. Variation of the substituents at the 3-position in the cephem nucleus, at the 2-position of the pyrimidine ring, and of the phenyl residue in the acyl side chain is carried out. Qualitative structure-activity relationships in this series are discussed.

Synthesis and antibacterial activity of pyrimidinylureidopenicillins.

The 6R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(4-hydroxyphenyl) acetamido]-penicillanic acids (10), prepared by two synthetic routes, exhibit broad antimicrobial activity against Gram-positive and Gram-negative bacteria. Their structure activity relationships are discussed. 6R-[(R)-2-[3-[2-(p-Aminosulfonyl)anilino-4-hydroxy-5-pyrimidinyl] ureido]-2-(4-hydroxyphenyl)acetamido]-penicillanic acid, sodium salt (VX-VC 43, 10m), the most active compound, shows very low MIC (minimal inhibitory concentration) values against clinically important Gram-negative bacteria, primarily Pseudomonas aeruginosa.

Modification of spectinomycin. 2. Derivatives of 4-dihydro-4-deoxy-4(R)-aminospectinomycin.

Acyl derivatives 5a approximately j and alkyl derivatives 7a approximately r of 4-dihydro-4-deoxy-4(R)-aminospectinomycin (1a) were prepared and tested for antibacterial activity. Only acyl compounds derived from long chain aliphatic acids showed activity in vitro, but were inactive when tested in vivo. All alkyl derivatives were active in vitro.