Asymmetric synthesis of BB-3497--a potent peptide deformylase inhibitor.
By screening a library of metalloenzyme inhibitors, the N-formyl-hydroxylamine derivative BB-3497 was identified as a potent inhibitor of Escherichia coli peptide deformylase with antibacterial activity both in vitro and in vivo. The homochiral synthesis of BB-3497, involving a novel asymmetric Michael addition reaction is described.
Pratt
L M
LM
British Biotech Pharmaceuticals Limited, Watlington Road, Cowley, Oxford OX4 6LY, UK. ayscough@britbio.co.uk
Beckett
R P
RP
Davies
S J
SJ
Launchbury
S B
SB
Miller
A
A
Spavold
Z M
ZM
Todd
R S
RS
Whittaker
M
M
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; C425109:BB3497; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin