The One-Step Synthesis of Biologically Active Isochromans from Lignin-Derived Aromatic Monomers in Tunable Deep...

Clean synthetic strategies that embrace the inherent structural features of renewable building blocks to obtain biologically active compounds hold great potential to improve the economic viability of emerging biorefineries. Importantly, such an approach is highly beneficial for the sustainable manufacturing of pharmaceutically relevant molecules. Here, we demonstrate a one-step protocol toward biologically active isochromans through the Oxa-Pictet cyclization involving both aromatic aldehydes, including vanillin, and aliphatic aldehydes in combination with lignin-derivable homovanillyl alcohol (1), a prominent aromatic platform chemical obtainable via diol-assisted fractionation. Employing tunable deep eutectic solvents as benign reaction media allows for modulating reactivity under mild reaction conditions, and opens access to a library of isochromans in a single step. Several compounds exhibit promising properties, including PPI inhibition, anticancer, and antibacterial activities, highlighting the benefits of this synthetic strategy and its potential for drug discovery.