Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete
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- 作者：Dagmara K. Derewacz ; C. Ruth McNees ; Giovanni Scalmani ; Cody L. Covington ; Ganesh Shanmugam ; Lawrence J. Marnett ; Prasad L. Polavarapu ; Brian O. Bachmann
- 刊名：Journal of Natural Products
- 出版年：2014
- 出版时间：August 22, 2014
- 年：2014
- 卷：77
- 期：8
- 页码：1759-1763
- 全文大小：257K
- ISSN：1520-6025
文摘
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鈥揇 (1鈥?b>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鈥搒olvent 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.