Synthesis of 7β-[(Z)-2-(2-Amimo-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic Acid (Ceftizoxime), a New Semisynthetic Cephalsporin Antibiotic. I. : An Improved Method for the Preparation of 7-Amino-3-methylene- and 7-amino-3-hydroxycepham-4-

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New synthetic methods for 7-amino-3-methylenecepham-4-carboxylic acid (X) and 7-amino-3-hydroxycepham-4-carboxylic acid (IX), which are key intermediates for the synthesis of ceftizoxime (I), were developed. These intermediates (IX and X) were synthesized without introducing any protecting groups at the C-7 amino and/or C-4 carboxylie acid groups of the cepham or cephem ring. Compound X was prepared from 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (XI) by zinc reduction either in aqueous or anhydrous neutral conditions. Compound IX was perpared from X by ozone oxidation at -75℃ followed by sodium borohydride at 0-10℃. A plausible mechanism of ozone oxidation of X is preseted, and the existence of an important intermediate, 7-amino-3-hydroxy-3-cephem-4-carboxylic acid (XXII), is demonstrated.
社団法人日本薬学会の論文
1988-02-25