TitlePrecursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus sp.
Publication TypeJournal Article
Year of Publication2021
AuthorsKhoshbakht M, Srey J, Adpressa DA, Jagels A, Loesgen S
Date Published2021 Jul 22

The plant endophyte 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.

Alternate JournalMolecules
PubMed ID34361574
PubMed Central IDPMC8347292
Grant ListR01 EB009772 / EB / NIBIB NIH HHS / United States
S10 OD018518 / OD / NIH HHS / United States
CHE 1808717/2020110 / / National Science Foundation /