title: Asymmetric synthesis of BB-3497--a potent peptide deformylase inhibitor.
abstract: 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.
authors.affiliation: British Biotech Pharmaceuticals Limited, Watlington Road, Cowley, Oxford OX4 6LY, UK. ayscough@britbio.co.uk
authors.forename: L M
authors.initials: LM
authors.lastname: Pratt
authors.forename: R P
authors.initials: RP
authors.lastname: Beckett
authors.forename: S J
authors.initials: SJ
authors.lastname: Davies
authors.forename: S B
authors.initials: SB
authors.lastname: Launchbury
authors.forename: A
authors.initials: A
authors.lastname: Miller
authors.forename: Z M
authors.initials: ZM
authors.lastname: Spavold
authors.forename: R S
authors.initials: RS
authors.lastname: Todd
authors.forename: M
authors.initials: M
authors.lastname: Whittaker
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; C425109:BB3497; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin