Synthetic Studies on b-Lactam Antibiotics. Part 5. A Synthesis of 7b-Acylamino-3-methyl-1-oxadethia-3-cephem-4-carboxylic Acids

Chloroazetidinone 10, prepared from 6-APA, was etherified with propargyl alcohol and zinc chloride to a 2:l mixture of cisand --ethers 18.The separated &-ether 18 was converted into a keto ylide -21d, which was cyclized by intramolecular Wittig reaction to 3-methyl 1-oxacephalosporin -22.From this compound, four optically active 3-methyl oxacephalosporins e -g were prepared.Interestingly all of them except -25d, 1-oxacephalexin, exhibited antibacterial activity as four to eight times high as that of the corresponding cephalosporins.