NOsynthese

NOSynthese is a term used to describe a suite of synthetic strategies aimed at constructing nitrogen-containing organic molecules through nitrogen-oxide intermediates. It covers enzymatic, chemoselective, and integrated chemoenzymatic routes that form N–O bonds or introduce N-oxide functionalities under mild conditions, with an emphasis on sustainability and step economy.

Origin and scope: The concept emerged as scientists sought unified frameworks for combining biocatalysis with chemical catalysis to access complex nitrogenous structures. NOSynthese typically involves designing cascades where an initial oxidation or nitrosation step creates an N–O intermediate that is subsequently transformed into the target motif through selective reductions, substitutions, or ring closures.

Methods: Approaches include biocatalytic steps using enzymes that generate or transfer nitrogen-oxide groups, transition-metal catalysis for N–O bond manipulation, and chemoenzymatic sequences performed in single reactors or continuous-flow setups. Advances in enzyme engineering, computational design, and process intensification have expanded substrate scope and improved selectivity.

Applications and significance: NOSynthese concepts have been applied to the synthesis of nitrogen heterocycles, pharmaceuticals, natural-product analogs, and functional materials. The approach aims to reduce protecting-group use, lower energy consumption, and enable late-stage modification of complex molecules.

Challenges and outlook: Areas of ongoing work include improving enzyme stability and turnover, achieving scalable production, and ensuring compatibility of biocatalytic steps with harsh chemical transformations. As methods mature, NOSynthese is expected to influence routes to active pharmaceutical ingredients and sustainable synthesis strategies.