Engineering Fluorine into Verticillins (Epipolythiodioxopiperazine Alkaloids) via Precursor-Directed Biosynthesis

  • J Nat Prod. 2019 Nov 22;82(11):3104-3110. doi: 10.1021/acs.jnatprod.9b00711.
Chiraz Soumia M Amrine  1 ,  Jessica L Long  1 ,  Huzefa A Raja  1 ,  Steven J Kurina  2 ,  Joanna E Burdette  2 ,  Cedric J Pearce  3 ,  Nicholas H Oberlies  1
Affiliations
  • 1. Department of Chemistry and Biochemistry , University of North Carolina at Greensboro , Greensboro , North Carolina 27402 , United States.
  • 2. Department of Pharmaceutical Sciences , University of Illinois at Chicago , Chicago , Illinois 60612 , United States.
  • 3. Mycosynthetix Inc. , 505 Meadowlands Drive, Suite 103 , Hillsborough , North Carolina 27278 , United States.
PMID: 31633350 DOI: 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.