Photocaged and Water‐Soluble Glucose Functionalization for Spatiotemporal Acidification Pathways

ABSTRACT The spatiotemporal control of complex molecular systems, such as chemical reaction networks (CRNs), requires reagents and reactive species that can be activated both efficiently and precisely. The design of CRNs has gained momentum as a strategy to investigate synthetic non‐equilibrium systems that mimic key features of biological processes operating far from thermodynamic equilibrium. In this study, we present a novel photocleavable and water‐soluble glucose–coumarin glycoside that bridges photochemical activation with chemical fuel‐driven reactivity. During the optimization of the peracetylated glucose–coumarin glycoside synthesis, we elucidate the reaction mechanism of the Koenigs–Knorr glycosylation and identify the most likely rate‐limiting step as the reversible formation of the orthoester. The photochemical release of glucose was subsequently used to drive an established model CRN based on glucose oxidase, enabling light‐triggered acidification of the aqueous environment. Given the high water solubility of the coumarin‐protected glucose derivative, our approach provides a versatile and easily implemented method for regulating pH‐responsive processes and assemblies through precise optical control, in a range of aqueous buffered media.