Electrochemical synthesis of self immolative methylene alkoxy carbamate (MAC) to facilitate construction of antibody drug conjugate linkers with alcohol-containing payloads

In the area of targeted drug delivery, the strategy of using Methylene alkoxy carbamate (MAC) as a self-immolative unit in the linker construction for antibody drug conjugate (ADC) has evolved as the most popular approach in recent time research. Reported synthetic routes for MAC linker construction are limited to very few options which often suffer synthetic challenges with diverse sets of alcohol-containing payloads. An alternative concept of constructing MAC linker employing electrochemical decarboxylative coupling strategy has been validated with a wide range of structurally different alcohols including primary, secondary and tertiary analogues, using DMA as a solvent. The model study allows using alcohol as a limiting reactant, extending the opportunity of utilizing different alcohol-containing payloads to conjugate via MAC to construct ADCs.