Work

Identification of Natural Isonitriles Through Ligation to an Azomethine Imine Probe

Year: 2026

Type: article

Abstract: Natural isonitriles are promising lead compounds for medicinal chemistry. Their identification is, however, challenging due to the hydrolytic lability of the isonitrile group. Here, we use the azomethine imine (AMI)-isonitrile ligation in a reactivity-based screening protocol for the chemoselective derivatization of natural isonitriles. The herein developed AMI probe rapidly reacts with isonitriles-primary, secondary, tertiary, as well as aromatic-to stable conjugates. A dibromide mass tag enables the detection of low-abundance isonitriles, even in complex biological matrices. The ligation establishes a new stereogenic center, thereby allowing facile distinction between achiral and chiral isonitriles by the formation of racemates or diastereoisomers, respectively. In addition, a unique reactivity of isonitriles bearing an α-COOH group was unraveled. This AMI probe enabled the detection of known bacterially produced isonitriles and the identification of a novel fungal isonitrile.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.202503642