Engineering Fluorine into Verticillins (Epipolythiodioxopiperazine Alkaloids) via Precursor-Directed Biosynthesis
- 21 October 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Natural Products
- Vol. 82 (11), 3104-3110
- https://doi.org/10.1021/acs.jnatprod.9b00711
Abstract
Precursor-directed biosynthesis was used to generate a series of fluorinated verticillins. The biosynthesis of these epipolythiodioxopiperazine alkaloids was monitored in situ via the droplet liquid microjunction surface sampling probe (droplet probe), and a suite of NMR and mass spectrometry data were used for their characterization. All analogues demonstrated nanomolar IC50 values vs a panel of cancer cell lines. This approach yielded new compounds that would be difficult to generate via synthesis.Keywords
Funding Information
- National Cancer Institute (P01 CA125066)
This publication has 53 references indexed in Scilit:
- Enantioselective Organocatalytic Fluorination‐Induced Wagner–Meerwein RearrangementAngewandte Chemie, 2013
- Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloidsChemical Science, 2013
- Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the BionectriaceaeThe Journal of Antibiotics, 2012
- Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspectsJournal of Enzyme Inhibition and Medicinal Chemistry, 2010
- Total Chemical Synthesis Peers into the Biosynthetic Black BoxScience, 2009
- Biosynthetic gene clusters for epipolythiodioxopiperazines in filamentous fungiMycological Research, 2008
- Fluorine in Pharmaceuticals: Looking Beyond IntuitionScience, 2007
- The Discovery of Fluoxetine Hydrochloride (Prozac)Nature Reviews Drug Discovery, 2005
- Fungal epipolythiodioxopiperazine toxins have therapeutic potential and roles in diseaseTrends in Pharmacological Sciences, 1987
- THE TREATMENT OF RHEUMATOID ARTHRITIS WITH ADRENO‐CORTICOSTEROIDS AND THEIR SYNTHETIC ANALOGUES: AN APPRAISAL OF CERTAIN DEVELOPMENTS OF THE PAST DECADE*Annals of the New York Academy of Sciences, 1959