Sesterterpenoids

Sesterterpenoids are a class of terpenoids containing 25 carbon atoms, derived from five isoprene units. They are designated as sesterterpenes and are formed in nature by sequential condensation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) units via the terpenoid biosynthetic pathways (mevalonate or MEP). The assembly typically extends a farnesyl or geranylgeranyl pyrophosphate backbone with additional IPP units and then undergoes cyclization by terpene synthases and post-synthetic modifications such as oxidation, reduction, glycosylation, and lactonization.

Structural diversity is high: sesterterpenoids exhibit a range of polycyclic and macrocyclic frameworks, often with multiple oxygen-containing functionalities. The best-known skeletons include ophiobolane-type and other polycyclic arrangements; many compounds possess epoxides, lactones, and hydroxyl groups. This structural complexity contributes to a broad array of biological activities.

Natural sources include fungi (particularly various ascomycetes), as well as some marine organisms and plants. Owing to their structural variety, sesterterpenoids are of interest for natural product chemistry and drug discovery, with ongoing research into discovery of new structures and understanding biosynthetic pathways.

Biological activities reported for sesterterpenoids cover antimicrobial, antifungal, anti-inflammatory, and cytotoxic effects, among others. Some compounds show potent activity against cancer cell lines, parasites, or pathogens, making them leads in medicinal chemistry. Research also focuses on chemoenzymatic synthesis and total synthesis to elucidate biosynthesis and to create analogs.