Precursor-Directed Identification of Natural Product Scaffolds
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The rapid generation of natural product analogs is a fundamental challenge in both the optimization of medicinal potency and exploration of novel biological activity. Previous work with Streptomyces variabilis has demonstrated that natural products that incorporate non-enzymatic transformation can be exploited for the rapid generation of analogs. Herein we demonstrate a general methodology to use fluorinated or isotopically labeled substrates to identify natural product frameworks prone to non-enzymatic pathways. As proof of principle our precursor directed methodology was used in the study of discoipyrrole A formation, the guided isolation of a novel iminoquinone and the detection of a novel ammosamide analog via incorporation of a carbon-based nucleophile.
Heterocyclic Compounds, 3-Ring