Recently, syntheses and antibacterial activity of 1-oxacephems have increasingly attracted attention. Christensen and co-workers synthesized dl-1-oxacephalothin (dl-1) and dl-1-oxacefamandole (dl-2), with dl-1 less potent than cephalothin and dl-2 twice as potent as cefamandole. Our previous work reported optically active 3-methyl-1-oxacephems 3 with four- to eightfold higher activity than their 1-thia congeners, prompting studies on optically active 3-substituted methyl-1-oxacephems and 7a-methoxy compounds (including 1-oxacephalothin (1), 1-oxacefamandole (2), 7a-methoxy-1-oxacefamandole O-formate (4), and the title compound 6059-S, the disodium salt of 5). Starting from azetidinone 6 (derived from 6-aminopenicillanic acid), we performed selective hydrogenation, epoxidation, epoxide ring cleavage, oxidation, side chain modification (ozonolysis, reduction, chlorination, triphenylphosphine treatment), heating, deacylation, 7α-methoxylation, acylation, and deprotection to synthesize these compounds. MIC values (Table I) demonstrated that these 1-oxacephems were four- to eightfold more potent than their 1-thia counterparts against most susceptible bacteria. The title compound, featuring a p-hydroxyphenylmalonylamido group at C7, exhibited excellent activity and a broadened spectrum against Gram-negative bacteria, including Pseudomonas aeruginosa and a β-lactamase-producing strain of Klebsiella pneumoniae.