Recent advances in late-stage monofluorination of natural products and their derivatives

Abstract

Natural products and their derivatives have always been an inspiration for drug discovery and are well known for their wide pharmacological activities, but there are still very few molecules on the market due to issues such as bioavailability, lipophilicity, and metabolism. Since late-stage functionalization has grown vastly in the past decades for the diversification of natural products and derivatives thereof, the late-stage monofluorination of these complex molecules has also been reported. As fluorine incorporation into an organic molecule can modulate its bioavailability, solubility, and pharmacological and pharmacodynamic properties relative to its non-fluorinated analogue, there has been a surge in the development of fluorine-containing molecules in the past few decades. Numerous strategies such as C–H bond functionalization (directed and non-directed), C–X bond cleavage, C–C bond cleavage and C–O bond cleavage for the monofluorination of organic molecules with fluorinating reagents having a nucleophilic, electrophilic or radical nature have been reported. In this review, we have covered the application of these strategies which primarily aims at C(sp³)–F and C(sp²)–F bond formation in natural products via late-stage functionalization involving C–H functionalization, and functional group transformation from 2011 to 2023.