Clean Synthetic Strategies to Biologically Active Molecules from Lignin: A Green Path to Drug Discovery**

Abstract

Deriving active pharmaceutical agents from renewable resources is crucial to increase the economic feasibility of modern biorefineries and promises to alleviate critical supply‐chain dependencies in pharma manufacturing. At the fundamental level, embracing the structural complexity of renewable resources offers hitherto unexploited opportunities for the green synthesis of essential pharmaceuticals, and opens new avenues in drug discovery. In this vein, our multidisciplinary approach combines research in lignin‐first biorefining, sustainable catalysis, and alternative solvents with bioactivity screening, an in vivo efficacy study, and a structural similarity search. The resulting sustainable path to novel anti‐infective, anti‐inflammatory, and anti‐cancer molecules enabled the rapid identification of frontrunners for key therapeutic indications. Most significantly, we discovered an anti‐infective against the priority pathogen Streptococcus pneumoniae, showing efficacy in vivo and promising plasma‐ and metabolic stability. Our established chemocatalytic methods, inspired by the innate structural features of lignin, provide straightforward access to synthetically challenging biologically active molecules of the core dopamine structure, namely tetrahydroisoquinolines, quinazolinones, 3‐arylindoles and the natural product tetrahydropapaveroline. Our diverse array of atom‐economic transformations produce only harmless side‐products and use benign reaction media, such as tunable deep eutectic solvents for modulating reactivity in challenging cyclization steps.

Lattice Strain Engineering on Metal‐Organic Frameworks by Ligand Doping to Boost the Electrocatalytic Biomass Valorization

“…These derivatives have been used in fungicides, antioxidants, anti-hardeners, drug intermediates, etc. [18][19][20][21][22] Nevertheless, the intricate molecular structure and inherent degradation resistance of lignin still hinder its depolymerization toward high-value utilization, especially through electrocatalytic process. Therefore, to break the depolymerization barrier for lignin valorization, enhancing the contact and adsorption between the electrocatalyst and reactant is of great importance.…”