Recent Advances in the Development of Targeted Activation Strategies for Organoboron Prodrugs

Abstract Elevated levels of reactive oxygen species (ROS) are a hallmark of varieties of diseases such as cancer, inflammation, and neurodegenerative disorders. Inspired by the discrepancy of ROS concentrations between pathological tissues and the normal counterparts, an increasing number of ROS‐responsive theragnostic prodrugs are developed in past years, with particularly high proportions of organoboron‐based prodrugs that can respond to H 2 O 2 . Unfortunately, increasing studies have demonstrated that the intrinsic ROS (H 2 O 2 ) levels in most pathological tissue are only slightly higher than normal tissues and are not adequate to activate organoboron prodrugs; in contrast, several organoboron compounds have been clinically approved in which boronic acid acts as electrophilic warhead. To this end, developing more robust and universal approaches for boronic acid‐prodrug activation becomes highly attractive. In this context, we discuss the recently reported activation strategies for boron‐caged prodrugs with a particular focus on their design principles and activation mechanisms. The perspectives on the future directions for this important research area are discussed as well.