Difluoromethylene analogues of aspartyl phosphate:: the first synthetic inhibitors of aspartate semi-aldehyde dehydrogenase

The difluoromethylene analogue of aspartyl phosphate 6 has been prepared by the fluoride catalysed coupling of diethyl trimethylsilyldifluoromethyl phosphonate with an appropriate aldehyde followed by Dess-Martin oxidation and deprotection; the deprotected compound inhibited (K-I 95 muM) aspartate semi-aldehyde dehydrogenase, a key enzyme involved in bacterial amino acid and peptidoglycan biosynthesis.