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 (KI 95 microM) aspartate semi-aldehyde dehydrogenase, a key enzyme involved in bacterial amino acid and peptidoglycan biosynthesis.
Cox
R J
RJ
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK. r.j.cox@bris.ac.uk
Hadfield
A T
AT
Mayo-Martín
M B
MB
D001223:Aspartate-Semialdehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure
C032197:beta-aspartyl phosphate; D001224:Aspartic Acid; D001223:Aspartate-Semialdehyde Dehydrogenase