title: Gold-Catalyzed Cyclization Leads to a Bridged Tetracyclic Indolenine that Represses β-Lactam Resistance.
abstract: A gold-catalyzed desilylative cyclization was developed for facile synthesis of bridged tetracyclic indolenines, a common motif in many natural indole alkaloids. An antimicrobial screen of the cyclization products identified one compound which selectively potentiates β-lactam antibiotics in methicillin-resistant S. aureus (MRSA), and re-sensitizes a variety of MRSA strains to β-lactams.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 (USA).
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 (USA).
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 (USA). xiang.wang@colorado.edu.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D015195:Drug Design; D004357:Drug Synergism; D006046:Gold / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy; D018440:beta-Lactam Resistance / Q000187:drug effects*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles; D047090:beta-Lactams; D006046:Gold
keywords: antibiotics; drug discovery; gold; heterocycles; synthetic methods