Natural product synthesis articles from across Nature Portfolio

Within the mint family, clary sage (Salvia sclarea) is the only species that produces sclareol, a pathogen defense diterpene. Here, the authors report a chromosome level clary sage genome, a genus level pangenome consisting of seven assemblies, and the gene underlying sclareol biosynthesis.

Natural products with densely fused polycyclic frameworks, such as dalesconols A and B, pose longstanding challenges for asymmetric synthesis due to their intricate stereochemistry. Here, the authors report concise, enantioselective total syntheses via a triple-relayed remote chirality transfer strategy using palladium/norbornene catalysis.

Flueggea suffruticosa produces structurally diverse Securinega alkaloids with complex dimeric frameworks. Here, the authors report the discovery of flueggeacosines D–F and securingine J, and their biosynthetically inspired syntheses.

The synthesis of multisubstituted furans is constrained by step-intensive, expensive, and inefficient methods. Here, the authors introduce an operationally simple Fe(III)-catalyzed [3 + 2]-annulation cascade of active methylenes and 3-oxetanone, enabling the efficient construction and diversification of furan architectures, with implications for the synthesis of bioactive natural products.

The mechanism underlying the formation of ionophore polyethers—polyketide-derived natural products containing tetrahydrofuran and tetrahydropyran rings—has been elusive. Now structural and biochemical analyses reveal that a C₂₆ linear precursor undergoes four successive cyclizations within the single active site of the heterodimeric polyether epoxide hydrolase MonBI·MonBII, in which MonBI promotes MonBII’s folded active conformation.

Ahead of his 80th birthday, Steven V. Ley, Professor of Chemistry at the University of Cambridge, discussed his career from drawing chemicals by hand to his work generating complex natural product architectures using machines.

Much natural-product-based drug discovery has depended on the practices of Indigenous Peoples, who have sometimes invested centuries of care into the cultivation and use of plant or fungal matter. However, the contributions of the original discoverers can be lost as the natural products are developed into pharmaceutical products.

Enantioselective hydrogenation is a stalwart reaction in synthetic chemistry. Now, hydrogenation of tetrasubstituted 1,2-dihydronaphthalene esters gives access to more than 30 cyclolignan natural products.

Owing to its structural complexity, the total synthesis of alchivemycin A has proved challenging. Now, the total synthesis of alchivemycin A is achieved using a chemoenzymatic approach that combines de novo skeleton construction with a late-stage enzymatic oxidation cascade. Following rational protein engineering of a key enzyme, the final product is obtained in high yield.