Directly linked 1,3-azoles are found as substructures in important naturally occurring products that have interesting biological activities as well as fascinating structures. Therefore, many research groups are working on their total syntheses. Although new approaches have been developed to prepare these targets, classical 1,3-azole formation methodologies are still being used for this purpose. This report provides an overview of polyazole-containing natural products and the different strategies for the synthesis of directly linked 1,3-azole moieties.

[structure: see text] An efficient and versatile convergent synthesis of IB-01211 based on a combination of peptide and heterocyclic chemistry is described. The key step in the synthesis is macrocyclization through intramolecular Hantzsch formation of the thiazole ring. Dehydration of a free primary alcohol to furnish the exocyclic methylidene present in the natural product was applied during the macrocyclization.

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The cytotoxicity of 1 and the synthesized analogues were evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives 2 and 3c were chosen for further studies on effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis were detected.