Modular synthetic routes to biologically active indoles from lignin

Abstract

Diol-assisted fractionation has emerged as an important ‘lignin-first’ processing method that delivers aromatic C2-acetals with high selectivity. This contribution describes the development of an unexpectedly straightforward synthetic route to biologically active indoles from this aromatic platform chemical, boosting the scope of this unique biorefinery approach. The novel method utilizes the functionalization of C2-acetal via phenol alkylation and mild halogenation reactions, enabling catalytic C–N coupling with anilines and benzylamines and forging ortho-aminoacetal intermediates. Such derivatives are suitable for in situ Schiff base formation/intramolecular cyclization by acetal deprotection in a mixture of MeOH/H₂O and PTSA as the catalyst, resulting in a novel library of lignin-based indoles. Evaluation of the biological activity in terms of anticancer activity using human Hep G2 cells shows promising early results.