Chemoenzymatic Relay Synthesis of Quinolines: Laccase/TEMPO/ D -Glucose-Based Ionic Salt/atm O 2 -Catalyzed Chemoselective Oxidation of 2-Aminobenzyl Alcohols

Laccases are widely applied as promising high-value enzymes for oxidation reactions. To provide more insight into this, we have developed a chemoenzymatic one-pot relay synthesis of quinolines incorporating a laccase/TEMPO system with a d -glucose-based ionic salt (GIS I – ) run under air at room temperature. The developed relay strategy involves a two-step process where laccase/TEMPO performs the oxidation of o -aminobenzyl alcohols, forming an o -aminobenzaldehyde intermediate, which is further annulated by coupling with active methylene groups in the presence of GIS I – . This methodology allows a straightforward synthesis of 26 aldehydes up to 88% yield and 30 quinolines up to 81% yield. To provide more insight into the developed synergistic system, the stability of laccase vs GIS I – was studied, and the results indicated that the developed GIS I – did not degrade the protein structure and stabilized the enzyme. Environmental acceptability metrics were calculated for the developed process with a commendable E-factor of 2.02 and an atom economy of 89.41%. The developed catalytic system was successfully employed for the gram-scale synthesis of the antibacterial agent indenoquinolinone in good yield, which can help in developing active pharmaceutical ingredients (APIs).