N-Heterocyclic Carbene Organocatalysis Enabled Modular Synthesis of Fluorinated Isoflavonoids to Suppress Proliferation and Migration in Breast Cancer Cells.

Abstract

Isoflavonoids represent a privileged scaffold among various bioactive natural products, rendering their structural diversification through green synthesis and subsequent biological evaluations a compelling research area. In this study, an NHC organocatalytic radical acylalkylation of 1,3-enynes using salicylaldehydes is presented, followed by a cascade intramolecular annulation, yielding a series of fluorinated isoflavone derivatives with substantial yields under environmental-friendly conditions. This approach, distinguished by its excellent modularity and high functional group tolerance, represents an unprecedented organocatalytic 1,3,4-trifunctionalization of 1,3-enynes designed for the green synthesis of bioactive isoflavones in a single step. Furthermore, it is demonstrated that these synthesized fluorinated isoflavonoids effectively suppress proliferation in breast cancer cells, with the most potent compound 8 also inhibiting migration in MDA-MB-231 cells.