Pharmaceutically relevant (hetero)cyclic compounds and natural products from lignin-derived monomers: Present and perspectives

Abstract

Lignin, the richest source of renewable aromatics on the planet, is an intriguing raw material for the construction of value-added aromatics. In the past decade, much progress has been made regarding the development of efficient lignin depolymerization methods, able to produce specific monophenol derivatives in high-enough selectivity and yields. This now serves as an excellent basis for developing powerful downstream conversion strategies toward a wide range of products, including fine chemical building blocks. The inherent structural features of lignin-derived platform chemicals undoubtedly inspire the development of novel, creative, atom-economic synthetic routes toward biologically active molecules or natural products. In this perspective we attempt to bridge the structural features of lignin-derived platform chemicals with existing synthetic strategies toward the construction of heterocycles and provide a summary of efforts for the production of natural products from aromatics that can be, in principle, obtained from lignin. Last, we comment on the latest efforts that present entire value-chains from wood to valuable pharmaceutically relevant compounds.

Keywords: Chemistry; Green Chemistry; Organic Chemistry; Process Biotechnology.

Graphical abstract

Figure 1

Overview of selected key platform chemicals obtained from different lignin depolymerization processes Compounds in gray do not belong to a pool of typical platform chemicals that are directly obtained by catalytic depolymerization.

Figure 2

Various classes of (hetero)cyclic compounds that could be potentially obtained through the functionalization of key lignin-derived platform chemicals (for more details see the supplemental information, Scheme S1)

Figure 3

Selected examples of natural products that could be in principle obtained from lignin-derived platform chemicals (besides neolignanes and lignans) In parenthesis the number of steps required to synthesize the target products and overall yields are specified. The corresponding biological activities are color coded.

Scheme 1

Key steps in the synthesis of selected natural products (A) Tylophorine. (B) Lupinalbin A. (C) Isoshonanin.

Figure 4

Various strategies to obtain pharmaceutically relevant compounds from lignocellulose (A) Example of a sustainable synthesis strategy of a biologically active molecule from bio-sourced precursors. (B) Overview of known pathways for the production of nitrogen-containing chemicals from lignin-derived platform chemicals obtained upon reductive catalytic fractionation (RCF).