Natural Product Synthesis and Pharmacological Bioactivity

Natural products, molecules derived from plants, microorganisms and marine organisms, have served as a rich source of therapeutic agents for centuries. Advances in total synthesis have enabled the recreation and modification of these complex structures, unlocking access to scarce compounds and their analogues. Asymmetric synthesis in particular has allowed precise control of stereochemistry, a critical factor in determining biological activity. Parallel to synthetic efforts, pharmacological bioactivity studies probe interactions with biological targets through assays ranging from enzymatic inhibition to cellular phenotyping. These investigations reveal modes of action—such as enzyme modulation, receptor binding and pathway interference—and define potency and selectivity through metrics like the minimum inhibitory concentration. Integrated approaches now combine synthetic methodology with high-throughput screening and mechanistic analysis to optimise lead compounds for antimicrobial, anticancer and anti-inflammatory applications. The global burden of drug resistance and emerging diseases continues to drive innovation at the interface of chemistry and biology, with natural product frameworks inspiring next-generation medicines.

Research from Nature Portfolio

Researchers have developed a concise asymmetric total synthesis of polycyclic xanthenes, enabling assembly of a benzopyrano-xanthene core with high diastereo- and enantioselectivity. The route employs a retro-hemiketalisation/double Michael cascade and a Mitsunobu-mediated chiral resolution, yielding an antibiotic candidate that activates the WalK sensory kinase and induces autolysis in drug-sensitive and multidrug-resistant Staphylococcus aureus strains. In a complementary study, novel meroterpenoids with unprecedented coupling of phloroglucinol and sesquiterpene units were isolated from tropical fruit. Detailed spectroscopic and computational analyses established their unique skeletons and plausible biosynthetic pathways, while in vitro assays demonstrated moderate cytotoxicity against human cancer cell lines, highlighting these scaffolds as leads for anticancer drug discovery.

Natural Product Synthesis and Pharmacological Bioactivity publication trend

The graph below shows the total number of articles in natural product synthesis and pharmacological bioactivity across all publications each year (not limited to Nature Index journals).

Technical terms

Natural product: A chemical compound produced by a living organism, often with complex structure and biological activity.

Asymmetric synthesis: A synthetic strategy that selectively generates one enantiomer of a chiral molecule.

Secondary metabolite: A non-essential small molecule produced by organisms for defence, signalling or ecological interactions, often with pharmacological properties.

Meroterpenoid: A hybrid natural product partly derived from terpenoid biosynthesis combined with non-terpenoid building blocks.

Minimum inhibitory concentration (MIC): The lowest concentration of a compound that prevents visible growth of a microorganism in vitro.

References

1. Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA. Nature Communications (2024).
2. Cytotoxic Meroterpenoids with Rare Skeletons from Psidium guajava Cultivated in Temperate Zone. Scientific Reports (2016).
3. Catalytic asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E. Chemical Science (2018).
4. Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds. Molecules (2016).
5. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines (2015).