Dictyodendrins are indole alkaloids isolated from marine sponges Dictyodendrilla verongiformis and Ianthella sp. Dictyodendrins A–E have been reported to inhibit the activity of telomerase, making them potential anticancer agents. Dictyodendrins F–J exhibited inhibitory activity towards β-site amyloid-cleaving enzyme 1 (BACE1), and are therefore recognized as potential targets for the treatment of Alzheimer’s disease. Dictyodendrins consist of a highly substituted pyrrolo[2,3-c]carbazole core, the complexity of which has attracted considerable interest of synthetic chemists. Several total syntheses of dictyodendrins have been reported to date, which rely on the introduction of several optimally placed substituents prior to the construction of the pyrrolo[2,3-c]carbazole core. We envisaged that the development of a diversity-oriented synthesis for the construction of these natural products based on the early-stage construction of the core structure, followed by the introduction of the different substituents, would be more amenable to medicinal applications. The key step in our total synthesis involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki–Miyaura coupling), C2 (addition to aldehyde), N3 (alkylation) and C5 (Ullman coupling) positions led to total syntheses of dictyodendrins B, C (formal), E (formal), and F.

Total synthesis of dictyodendrins by the gold-catalyzed intermolecular cascade cyclization of conjugated diynes with pyrroles

254th National Meeting (2017)

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