Assignment of the liposidomycin diazepanone stereochemistry

The liposidomycins comprise a family of complex nucleoside antibiotics that inhibit bacterial peptidoglycan synthesis. Their structures (1, 2) feature nucleoside, ribofuranoside, diazepanone, and lipid regions. Several stereo genic centers remain unassigned, including three within the diazepanone reg ion: C-6', C-2"', and C-3"'. An intramolecular reductive amination reaction has been used to prepare model diazepanones. Analysis of 40 and two of its diastereomers by NMR spectroscopy, X-ray crystallography, and molecular mo deling indicates a close relative configurational and conformational match between 40 and the liposidomycin diazepanone degradation product 43 and all ows the assignment of stereochemistry of the natural products as either [C- 6'(R), C-2''' (R), C-3''' (R)] or [C-6'(S), C-2'''(S), C-3'''(S)].