Natural Product Chemistry of p-Terphenyl Metabolites

p-Terphenyl metabolites constitute a distinctive class of aromatic polyketides characterised by a linear 1,4-diaryl-substituted benzene core. These compounds arise predominantly from fungal biosynthetic pathways, in which iterative polyketide synthases catalyse chain elongation and cyclisation to yield the central benzene ring and its flanking phenyl units. Subsequent tailoring enzymes introduce a diversity of substituents, including hydroxyl, methoxy, prenyl and glycosyl moieties, affording an extensive structural repertoire. This chemical versatility underpins a broad spectrum of biological activities, from antimicrobial and cytotoxic effects to enzyme inhibition and antiviral properties. The elucidation of p-terphenyl structures has relied on integrated spectroscopic techniques—principally high-resolution mass spectrometry and multidimensional nuclear magnetic resonance spectroscopy—often complemented by X-ray crystallography and computational methods for stereochemical assignment. Advances in genome mining and heterologous expression have begun to reveal the genetic and enzymatic basis of p-terphenyl biogenesis, enabling pathway engineering for enhanced yield and novel analogue production. Given their potent pharmacological profiles and amenability to synthetic modification, p-terphenyls are emerging as lead structures in drug discovery, agrochemical development and chemical biology research, with global relevance to human health and industry.

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Natural Product Chemistry of p-Terphenyl Metabolites publication trend

The graph below shows the total number of articles in natural product chemistry of p-terphenyl metabolites across all publications each year (not limited to Nature Index journals).

Technical terms

p-Terphenyl: An aromatic scaffold comprising three benzene rings linked in para positions to form a linear tricyclic core.

Polyketide synthase (PKS): A multifunctional enzyme complex that assembles polyketide chains through successive condensations of acyl-CoA units.

Nuclear magnetic resonance (NMR) spectroscopy: An analytical technique that exploits magnetic properties of nuclei to determine molecular structure and stereochemistry.

IC₅₀: The concentration of a compound required to inhibit a given biological or biochemical function by 50 percent.

Endophytic fungus: A fungus that lives within a plant host without causing disease, often producing unique secondary metabolites.

References

1. p-Terphenyl and Diphenyl Ether Derivatives from the Marine-Derived Fungus Aspergillus candidus HM5-4. Marine Drugs (2023).
2. Polyhydroxy p-Terphenyls from a Mangrove Endophytic Fungus Aspergillus candidus LDJ-5. Marine Drugs (2021).
3. Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1. Marine Drugs (2022).