Nuclear modification of clavulanic acid. The preparation of two 4,7-fused β-lactam systems

Abstract

The 4,7-fused β-lactam compounds benzyl 3-methoxy-9-oxo-6-oxa-1-azabicyclo[5.2.0]non-2-ene-2-carboxylate and benzyl 3-methoxy-9-oxo-6-oxa-1-azabicyclo[5.2.0]nona-2,4-diene-2-carboxylate have been prepared by routes which utilise the total carbon–oxygen skeleton of benzyl clavulanate (2). The corresponding 4-nitrobenzyl esters were similarly prepared from 4-nitrobenzyl clavulanate and these were converted into the lithium carboxylates via hydrogenolysis. In an unsuccessful attempt to prepare one of these 4,7-fused ring systems, compound (2) was found to react with triethylamine to give two 14-membered ring compounds, dibenzyl (7RS, 16RS)-3,12-dihydroxy-9,18-dioxo-6,15-dioxa-1,10-diazatricyclo[14.2.0.0^7,10]octadeca-2,11-diene-2,11-dicarboxylate and its (7RS, 16SR)-isomer.