A solvent‐free, catalyst‐free formal [3+3] cycloaddition dearomatization strategy: towards new fluorophores for biomolecules labelling

Overview & Synopsis

A general, sustainable dearomatization reaction for nitrogen-containing heterocycles was developed. Under solvent free conditions and without catalyst, the biorenewable methyl coumalate (MC) reacts as an efficient C3 partner to convert nine types of basic aromatic rings into their pyrido[1,2-a] fused derivatives in good to excellent yields. The fluorescence properties of some of the products were harnessed to conjugate fluorescent tags to BSA and immunoglobulin G. The extensive use of synthetic fluorophores in biological imaging [1] makes them prime candidates in organic synthesis projects. This photophysical property is interesting for the labelling of biomolecules such as amino acids, peptides, proteins, and DNA. In general, fluorescent organic skeletons contain polycyclic conjugated systems with mobile electrons, see for instance BODIPYs, rhodamines, 1,8-naphtalamides, fluoresceins and oxadiazoles. [2] These electronic characteristics may sometimes allow, after interaction with the target, a change in the fluorescence properties. In this article we present the synthesis of such platforms with such electronics features, based on the dearomatization of pyridine or other nitrogen-based aromatics.