RESUMEN
The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical medicinal chemistry library screen. Ring-closing metathesis, lactonisation and SmI2 -mediated methods were exemplified and applied to the installation of a third ring to mimic the nine-membered ring of the 2,11-cembranoids. The library was assessed for aqueous solubility and permeability, with a chemical-space analysis performed for comparison to the family of cembranoid natural products and a sample set of a screening library. Preliminary investigations in cancer cells showed that the simpler scaffolds could recapitulate the reported anti-migratory activity of the natural products.
Asunto(s)
Benzofuranos/química , Productos Biológicos/síntesis química , Diterpenos/síntesis química , Lactonas/química , Bibliotecas de Moléculas Pequeñas/química , Productos Biológicos/química , Química Farmacéutica , Diterpenos/químicaRESUMEN
The 2,11-cyclized cembranoids are isolated from marine invertebrates of Octocorallia species. They are a very interesting class of natural products sharing a common oxatricyclo[6.6.1.0(2,7)]pentadecane core and carrying a varied substituent pattern. This review presents their structural diversity along with the reported biological activities. The 2,11-cyclized cembranoids were comprehensively reviewed previously in 1998, and this contribution will serve as an update of that work. Since 1998 a number of structural assignments of the isolated products have been revised, some as a result of total synthesis efforts. The chemical reactivity of several of the natural compounds has been studied, and the relevance of these findings to the biosynthesis or the generation of isolation artifacts is discussed. The wide range of biological activities displayed by the 2,11-cyclized cembranoids justifies the interest shown within the synthetic chemistry community and suggests that this class of natural products remains a fruitful area for future synthetic and biological research.