Natural Products as Chemical Probes

Although more than 50% of the marketed drugs are based on natural products (NPs) or derivatives thereof, the small quantities in which these valuable molecules can be obtained from their natural sources poses a big limitation to future NPbased drug development. Laboratory synthesis is key, not only to provide enough quantities of NPs for biological applications, but also to optimize these compounds establishing the adequate pharmacological profiles for future use as clinical tools.
 

Total Synthesis of Iriomoteolide 3a

Marine ecosystems are a very prolific source of secondary metabolites. Recently, the Amphidiniumstrain HYA024 was found to produce structurally unique cytotoxic compounds such as Iriomoteolides 1a-c, as well as a rare 15-membered macrolide, Iriomoteolide-3a. From a synthetic perspective, these molecules offered interesting challenges, as eight chiral centers, four of them located in allylic positions, needed to be efficiently installed. Iriomoteolide and its synthetic derivatives were profiled against a small panel of cancer cell lines, with promising results. Furthermore, we have embarked in a chemical biology campaign to identify the cellular targets of these molecules.

Publications:

• R. Cribiú, C. Jäger, C. Nevado
  Angew.Chem. Int. Ed. (2009), 48, 8780