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Publisher Summary This chapter discusses the new antibacterial agents, antimicrobial agents, and various aspects of antimicrobial chemotherapy. The orally active third generation cephalosporin FK 027 (FR 17027) continued to be extensively studied in vitro and in vivo . Oral administration of cefuroxime axetil, the 1-acetoxyethyl ester prodrug of cefuroxime, to human volunteers produced higher peak serum levels than an equivalent dose of ampicillin and urinary recovery of 35%. Novel oxacephem derivative (6315-S,7), exhibited broad, potent anti-bacterial spectrum with the exception of activity against Pseudornonas . The effect on antibacterial activity of α-substituents in the 2-(2-amino-4-thiazolyl)acetyl side chain of ceftizoxime had been of great interest to the researchers working on anti-bacteraial agents. Reviews and symposiums on this topic project penicillin as orally effective prodrug, delivering good blood levels of temocillin after oral administration to human volunteer. The chapter discusses the role of carbupenems, β-lactarnuse inhibitors, aminoglycosides, and other associated compounds and antibacterial agents. Interest remained high in the synthesis of nalidixic acid analogs. Rosoxacin derivative win 35,349 showed good activity in vitro and in vivo against strains of Staphylococcus aureus and epidennidus. Because of the improved potency and spectrum, most efforts were centered on 6-fluoro analogs of pipemidic acid. Pefloxacin (1589 RB, 39) penetrated inflammatory cerebrospinal fluid at effective anti-bacterial levels after oral or parenteral administration in patients with bacterial meningitis.

— Various aspects of the 1-oxa-1-dethia-cephem syntheses starting from penicillins are discussed, especially, from the viewpoint of industrial production. Consideration of several approaches showed that the approach via the intermediate a (Scheme 5) was the most efficient and industrially feasible. In this route, stereocontrol is effected by intramolecular alcoholysis of the enantio-oxazolinoazetidinone derivative 68 giving the 7- epi -3-methylene-1-oxacepham nucleus 56 . Some improvements for conversion of the allylic iodide 67 into the allylic alcohol 68 are described, among which peracid oxidation of 67 to 68 was found to be the most advantageous. Interestingly, a new [2,3]-sigmatropic rearrangement of the allylic iodoso compound is involved in this oxidation reaction, which was developed into a new, general method for preparing the rearranged allylic alcohols from the allylic iodides. New methods are also introduced for converting the 7- epi -3-methylene-1-oxacepham nucleus 56 into various 1-oxacephem antibiotics including latamoxef (moxalactam, 6059-S) 12 . One of these methods offers the advantage of forming the 3(4)-double bond at the final step after completing the necessary functionalization at positions 3′ and 7 on 1-oxa cepham intermediates which are generally more stable to nucleophiles than 1-oxa-3- cephem analogs.