Open AccessEngineering Fluorine into Verticillins (Epipolythiodioxopiperazine Alkaloids) via Precursor-Directed Biosynthesis
Author(s) -
Chiraz Soumia M. Amrine,
Jessica L. Long,
Huzefa A. Raja,
Steven J. Kurina,
Joanna E. Burdette,
Cedric J. Pearce,
Nicholas H. Oberlies
Publication year - 2019
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.9b00711
Subject(s) - biosynthesis , chemistry , mass spectrometry , chemical synthesis , stereochemistry , cancer cell lines , combinatorial chemistry , organic chemistry , biochemistry , cancer cell , in vitro , chromatography , biology , enzyme , cancer , genetics
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 IC 50 values vs a panel of cancer cell lines. This approach yielded new compounds that would be difficult to generate via synthesis.