ISOXAZOLIDIN-5-ONE ANALOGS OF BETA-LACTAM ANTIBIOTICS

Isoxazolidin-5-ones, readily available via conjugate addition-rearrang ement of hydroxylamine to alpha,beta-unsaturated sugar 1,5-lactones, r eact with aldehydes and diethoxymethyl acetate to afford 2,4,5-trisubs tituted 1-aza-3,9-dioxa-8-oxo-bicyclo[4.3.0]nonanes. 4,5-Disubstituted toxycarbonyl-3,9-dioxa-8-oxo-bicyclo[4.3.0]nonanes undergo base-catal yzed rearrangement to 4,6-disubstituted butyl -dideoxy-3-N-oxamate-D-r ibohexaldono-1,5-lactones. The configuration of representative compoun ds: (2S,4R,5S,6S) -aza-3,9-dioxo-2-methyl-8-oxo-bicyclo[4.3.0]nonane a nd butyl ,3-dideoxy-3-N-oxamate-D-ribohexaldono-1,5-lactone were prove d by X-ray crystallography. (C) 1998 Elsevier Science Ltd. All rights reserved.