Title | Precursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus sp. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Khoshbakht M, Srey J, Adpressa DA, Jagels A, Loesgen S |
Journal | Molecules |
Volume | 26 |
Issue | 15 |
Date Published | 2021 Jul 22 |
ISSN | 1420-3049 |
Abstract | 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. |
DOI | 10.3390/molecules26154418 |
Alternate Journal | Molecules |
PubMed ID | 34361574 |
PubMed Central ID | PMC8347292 |
Grant List | R01 EB009772 / EB / NIBIB NIH HHS / United States S10 OD018518 / OD / NIH HHS / United States CHE 1808717/2020110 / / National Science Foundation / |