From lactols to lactones: Oxidative strategies for valuable pharmaceutical and industrial relevant compounds

Lactols are cyclic hemiacetals that are key intermediates in the synthesis of lactones, a class of compounds of great importance in the pharmaceutical, polymer, and fine chemical industries. The oxidative conversion of lactols to lactones has historically relied on stoichiometric chemical oxidants, often associated with limited selectivity, adverse conditions, and environmental problems. In recent decades, significant progress has been made in developing more selective, catalytic, and sustainable oxidative strategies. Biocatalysis has become a particularly attractive strategy for oxidative lactonization due to its inherent chemo-, regio-, and stereoselectivity, as well as its compatibility with mild and sustainable reaction conditions. This review provides a comprehensive overview of chemical and biocatalytic methodologies for the oxidation of lactols to lactones. Classical chemical approaches based on halogen reagents and transition metal-mediated systems are discussed with respect to their mechanism, scope, selectivity, and scalability. Special emphasis is placed on recent developments in biocatalysis, focusing on the role of oxidoreductases, such as alcohol dehydrogenases, aldehyde dehydrogenases, oxidases, and laccases, including the oxidation of diols via transient lactol intermediates and the direct oxidation of preformed lactols. Recent advances in enzyme engineering, cofactor regeneration strategies, and process design have enabled the biocatalytic oxidation of lactols to achieve high conversions, excellent enantioselectivities, and productivity relevant to industry, particularly in the synthesis of side-chain intermediates of statins and other high-value lactones.