From Wood to Tetrahydro-2-benzazepines in Three Waste-Free Steps: Modular Synthesis of Biologically Active Lignin-Derived Scaffolds

Abstract

Inherently complex, lignin-derived aromatic monomers comprising valuable structural moieties present in many pharmaceuticals would serve as ideal substrates for the construction of biologically active molecules. Here, we describe a strategy that incorporates all intrinsic functional groups present in platform chemicals obtained by lignin depolymerization into value-added amines, using sustainable catalytic methods and benign solvents. Our strikingly efficient protocol provides access to libraries of aminoalkyl-phenol derivatives and seven-membered N-heterocycles directly from wood in two, respectively three, waste-free steps. Several molecules in these libraries have shown promising antibacterial or anticancer activities, emphasizing the advantage of this modular synthetic strategy and the potential for drug discovery. The sustainable catalytic pathways presented here can lead to significant benefits for the pharmaceutical industry where reduction of hazardous waste is a prime concern, and the described strategies that lead to high-value products from non-edible biomass waste streams also markedly increase the economic feasibility of lignocellulosic biorefineries.