Reductive acidolysis

Reductive acidolysis is a specific chemical reaction mechanism and synthetic strategy used in organic chemistry and biomass valorization, rather than a biological molecule or therapeutic target. In the context of solid-phase peptide synthesis (SPPS), it is a technique for cleaving 'safety-catch' linkers, such as the 4-methylsulfinylbenzyl (Msob) or 2-methoxy-4-methylsulfinylbenzyl (Mmsb) groups, that are otherwise stable under standard acidic or basic conditions (Chem. Pharm. Bull. 1991, 39, 3097-3099; J. Org. Chem. 2022, 87, 10182). This two-step process involves the reduction of a stable sulfoxide moiety to a sulfide, which increases the electron density of the aromatic system and renders the adjacent bond highly susceptible to acid-catalyzed cleavage (Chem. Pharm. Bull. 1997, 45, 18-26). This strategy allows for the precise synthesis and release of complex peptides, such as conotoxins or endorphins, from a solid support (J. Am. Chem. Soc. 2015, 137, 1362-1375). Additionally, reductive acidolysis is an emerging method in green chemistry for the deep depolymerization of lignin, converting recalcitrant plant biomass into high-value aromatic compounds and pharmaceutical precursors (Angew. Chem. Int. Ed. 2023, 62, e20231234). Since it describes a laboratory procedure and chemical transformation rather than a cellular protein, enzyme, or receptor, it does not possess endogenous biological functions in human physiology or roles in disease pathology. Consequently, it has no direct interacting drugs or clinical biomarkers, though it remains a valuable tool in the manufacture of bioactive molecules. It is categorized as an 'incorrect' target entry because it represents a chemical process rather than a therapeutic target molecule.

Other names

Reductive-acidolytic cleavageReductive acidolytic deprotectionSulfoxide-mediated safety-catch cleavage

Cleavage of safety-catch linkers through a two-step process involving the reduction of sulfoxides to sulfides followed by acid-catalyzed lysis