No abstract

This review focuses on all known natural products that contain a "heteroatom-rich" ring system, specifically a five-, six- or seven-membered ring that contains three or more heteroatoms. The isolation and biological activity of these natural products is discussed, along with the biosynthetic processes that Nature employs to assemble these rare heterocyclic frameworks.

Synthesis of the 1,2,4-thiadiazole alkaloids polycarpathiamines A and B is described. The heteroaromatic core of the natural products was assembled using a one-pot benzylic oxidation–oxidative heterocyclization process.

The first syntheses of the bioactive cyclic tetrapeptide natural products, endolides A and B, were accomplished using a solution-phase macrocyclisation reaction; the stereoselectivity of which was found to be reagent-controlled.

A biomimetic thio-Diels-Alder reaction between a dienylthiadiazole and 3-thioisatin leads to the Isatis indigotica-derived alkaloid (1), along with its diastereomer 2. This synthetic study, supported by molecular modeling, establishes the viability of the proposed biosynthesis by thio-Diels-Alder cycloaddition, a very rare reaction in nature. Moreover, the results described infer that the diastereomer 2 is an as-yet undiscovered natural product present in Isatis indigotica.