title: Asymmetric Alkylation of Anthrones, Enantioselective Total Synthesis of (-)- and (+)-Viridicatumtoxins B and Analogues Thereof: Absolute Configuration and Potent Antibacterial Agents.
abstract: A phase transfer catalyzed asymmetric alkylation of anthrones with cyclic allylic bromides using quinidine- or quinine-derived catalysts is described. Utilizing mild basic conditions and as low as 0.5 mol % catalyst loading, and achieving up to >99:1 dr selectivity, this asymmetric reaction was successfully applied to produce enantioselectively (-)- and (+)-viridicatumtoxins B, and thus allowed assignment of the absolute configuration of this naturally occurring antibiotic. While the developed asymmetric synthesis of C10 substituted anthrones is anticipated to find wider applications in organic synthesis, its immediate application to the construction of a variety of designed enantiopure analogues of viridicatumtoxin B led to the discovery of highly potent, yet simpler analogues of the molecule. These studies are expected to facilitate drug discovery and development efforts toward new antibacterial agents.
authors.affiliation: Department of Chemistry, BioScience Research Collaborative and ‡Department of Biochemistry and Cell Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: K C
authors.identifier: 0000-0001-5332-2511
authors.initials: KC
authors.lastname: Nicolaou
authors.affiliation: Department of Chemistry, BioScience Research Collaborative and ‡Department of Biochemistry and Cell Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Guodu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Chemistry, BioScience Research Collaborative and ‡Department of Biochemistry and Cell Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beabout
authors.affiliation: Department of Chemistry, BioScience Research Collaborative and ‡Department of Biochemistry and Cell Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Megan D
authors.initials: MD
authors.lastname: McCurry
authors.affiliation: Department of Chemistry, BioScience Research Collaborative and ‡Department of Biochemistry and Cell Biology, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Yousif
authors.identifier: 0000-0001-9241-8962
authors.initials: Y
authors.lastname: Shamoo
mesh_terms: D000478:Alkylation; D000873:Anthracenes / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013754:Tetracyclines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D000900:Anti-Bacterial Agents; D013754:Tetracyclines; C539435:viridicatumtoxin B