title: Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase inhibitor produced by Penicillium verrucosum.
abstract: A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. min.chu@spcorp.com
authors.forename: Min
authors.initials: M
authors.lastname: Chu
authors.forename: Ronald
authors.initials: R
authors.lastname: Mierzwa
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Joseph
authors.initials: J
authors.lastname: Terracciano
authors.forename: Mahesh
authors.initials: M
authors.lastname: Patel
authors.forename: Vincent
authors.initials: V
authors.lastname: Gullo
authors.forename: Todd
authors.initials: T
authors.lastname: Black
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhao
authors.forename: Tze-Ming
authors.initials: TM
authors.lastname: Chan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McPhail
mesh_terms: D001130:Arizona; D018360:Crystallography, X-Ray; D019915:DNA Primase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005285:Fermentation; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; C482741:Sch 642305; D019915:DNA Primase