Electrochemical Carboxylic Acid Exchange for Sustainable Drug Development

Objective

Carboxylic acids are among the most common functional groups in approved drugs, yet their polarity and metabolic instability often compromise pharmacokinetics and limit clinical translation. Medicinal chemists routinely replace them with bioisosteres or extend their carbon chain, but existing methods rely on hazardous reagents, toxic intermediates, or unsustainable transition-metal catalysis. The eCARB-X project pioneers a unified, metal-free electrochemical platform that expands Kolbe-type reactivity into three transformative domains: (i) direct conversion of carboxylic acids into drug-relevant bioisosteres (trifluoromethyl ketones, sulfonamides, tetrazoles), (ii) safe one-carbon homologation as an alternative to diazomethane, and (iii) decarboxylative alkenylation via chalcogen linchpins. Mechanistic mapping (fast-scan CV, kinetics, DFT) will generate predictive rules that accelerate optimisation and scope, while translation to continuous-flow systems will ensure scalability, reproducibility, and industrial relevance. By introducing redox-based retrosynthetic logic, eCARB-X will deliver scalable and sustainable synthetic tools, directly supporting the European Green Deal and enabling greener drug discovery pipelines.