title: Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer.
abstract: Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.
authors.affiliation: Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Skraba-Joiner
authors.affiliation: The University of Queensland, Institute of Molecular Bioscience, 306 Carmody Road, St Lucia, Queensland 4072, Australia.
authors.forename: Zeinab G
authors.initials: ZG
authors.lastname: Khalil
authors.affiliation: Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: The University of Queensland, Institute of Molecular Bioscience, 306 Carmody Road, St Lucia, Queensland 4072, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
authors.affiliation: Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts 02215, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Porco
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C486291:rugulotrosin A