Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete.

Derewacz DK, McNees CR, Scalmani G, Covington CL, Shanmugam G, Marnett LJ, Polavarapu PL, Bachmann BO
J Nat Prod. 2014 77 (8): 1759-63

PMID: 25046128 · PMCID: PMC4334282 · DOI:10.1021/np400742p

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.

MeSH Terms (11)

Actinobacteria Caves Circular Dichroism Humans Models, Molecular Molecular Conformation Molecular Structure Naphthoquinones Nuclear Magnetic Resonance, Biomolecular Optical Rotatory Dispersion Stereoisomerism

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