Synthesis of novel fused β-lactams by intramolecular 1,3-dipolar cycloadditions. Part 10. The 9-oxo-6-thia-1,3-diazabicyclo[5.2.0]nonene, 8-oxo-5-thia-1,3-diazabicyclo[4.2.0]octene, and 8-oxo-5-oxa-1,3-diazabicyclo[4.2.0]octene ring systems

Abstract

4-Acetoxyazetidin-2-one (6) has been converted into (E)- and (Z)-1-[azido(t-butoxycarbonyl)methyl]-[2-(ethoxycarbonyl)vinylthio]azetidin-2-one (10) and (13). Thermolysis of either geometrical isomer in refluxing xylene afforded t-butyl (2RS,6RS)-4-ethoxycarbonylmethyl-8-oxo-5-thia-1,3-diaza-bicyclo[4.2.0]oct-3-ene-2-carboxylate (17) and both C-2 epimers of 5-ethoxycarbonyl-9-oxo-6-thia-1,3-diazabicyclo[5.2.0]non-4-ene-2-carboxylate (14) and (15).

The penicillin-derived (3S,4S)-4-acetoxy-3-phenoxyacetamidoazetidin-2-one (22) has been used to prepare (1 RS,3S,4R)-1-[azido(benzyloxycarbonyl)methyl]-4-prop-1-enyloxy-3-phenoxyacetamido-azetidin-2-one (27), which when heated in refluxing toluene gave benzyl (2S,6R,7S)-4-ethyl-8-oxo-7-phenoxy-acetamido-5-oxa-1,3-diazabicyclo[4.2.0]oct-3-ene-2-carboxylate (29). The corresponding free acid (30) was antibacterially inactive.