title: Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete.
abstract: Culture extracts from the cave-derived actinomycete Nonomuraea specus were investigated, resulting in the discovery of a new S-bridged pyronaphthoquinone dimer and its monomeric progenitors designated hypogeamicins A-D (1-4). The structures were elucidated using NMR spectroscopy, and the relative stereochemistries of the pyrans were inferred using NOE and comparison to previously reported compounds. Absolute stereochemistry was determined using quantum chemical calculations of specific rotation and vibrational and electronic circular dichroism spectra, after an extensive conformational search and including solute-solvent polarization effects, and comparing with the corresponding experimental data for the monomeric congeners. Interestingly, the dimeric hypogeamicin A (1) was found to be cytotoxic to the colon cancer derived cell line TCT-1 at low micromolar ranges, but not bacteria, whereas the monomeric precursors possessed antibiotic activity but no significant TCT-1 cytotoxicity.
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Dagmara K
authors.initials: DK
authors.lastname: Derewacz
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: C Ruth
authors.initials: CR
authors.lastname: McNees
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scalmani
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Cody L
authors.initials: CL
authors.lastname: Covington
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Shanmugam
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Prasad L
authors.initials: PL
authors.lastname: Polavarapu
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Bachmann
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D059552:Caves; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009905:Optical Rotatory Dispersion; D013237:Stereoisomerism
chemical_list: D009285:Naphthoquinones; C000601887:hypogeamicin A