Precursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus Chalara sp. |
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Authors: | Mahsa Khoshbakht Jason Srey Donovon A Adpressa Annika Jagels Sandra Loesgen |
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Institution: | 1.Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA; (M.K.); (J.S.); (D.A.A.);2.Whitney Laboratory for Marine Bioscience, Department of Chemistry, University of Florida, Gainesville, FL 32080, USA; |
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Abstract: | The plant endophyte Chalara sp. is able to biotransform the epigenetic modifier vorinostat to form unique, aniline-containing polyketides named chalanilines. Here, we sought to expand the chemical diversity of chalaniline A-type molecules by changing the aniline moiety in the precursor vorinostat. In total, twenty-three different vorinostat analogs were prepared via two-step synthesis, and nineteen were incorporated by the fungus into polyketides. The highest yielding substrates were selected for large-scale precursor-directed biosynthesis and five novel compounds, including two fluorinated chalanilines, were isolated, purified, and structurally characterized. Structure elucidation relied on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry. All compounds were tested for their bioactivity but were not active in antimicrobial or cell viability assays. Aminofulvene-containing natural products are rare, and this high-yielding, precursor-directed process allows for the diversification of this class of compounds. |
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Keywords: | precursor-directed biosynthesis fungal metabolite aminofulvenes biotransformation |
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