Chemical Modification of Sulfazecin. Synthesis of 4-Methoxycarbonyl-2-azetidinone-l-sulfonic Acid Derivatives1)

Abstract

In the course of the chemical modification of sulfazecin, 3-[2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)acetamido]-4-methoxycarbonyl-2-azetidinone-l-sulfonic acids were synthesized starting from cw-l-(2,4-dimethoxybenzyl)-4-methoxycarbonyl-3-phthalimido-2-azetidinone (2). These new 4-substituted derivatives showed more potent antimicrobial activities against gram-negative bacteria than did the corresponding 4-unsubstituted compounds, and the derivatives having 3,4-cis stereochemistry were more active than the trans isomers, especially against P. aeruginosa and some β-lactamase-producing bacteria. The reported procedure for the cycloaddition reaction used to prepare 2 was investigated in detail; by the use of a 20% excess of triethylamine, 2 was easily obtained in the yield of 72% as colorless crystals. A possible intermediate of β-lactam formation in this cycloaddition reaction, an acyl iminium salt (6), was isolated as crystals and converted into β-lactams by treatment with l,8-diazabicyclo[5.4.0]-7-undecene. © 1984, The Pharmaceutical Society of Japan. All rights reserved.