Total Synthesis of Curvicollid C

• Applicant: Professor Dr. Martin Hiersemann
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246978400

The elucidation of the configuration of natural products and the supply of derivatives for biological studies is of premiere importance. In this regard, the aim of the present project is to establish an enantioselective total synthesis of curvicollide C, a polyketide isolated from the mycoparasitic fungi Podospora curvicolla. Our extensive exploratory efforts have culminated into the credible research proposal at hand which defines important and interesting scientific questions.The isolation and structural elucidation of the C26-curvicollides A-C was first reported by Gloer et al. in 2004.The relative configuration of the polyketide was only partially elucidated and the absolute configuration remains unknown. Our project is aimed at the elucidation of the absolute configuration of curvicollide C by total synthesis of diastereomers of the natural product and their characterization by chiroptical methods. Furthermore, since it has been reported that curvicollide A shows promising antifungal activities but curvicollide C could not be tested due to lack of material, providing access to the natural product and derivatives thereof would enable a comprehensive biological study. The unique constitution of the curvicollides implicates a rather unusual biosynthetic pathway in which the carbon backbone of the curvicollides is assembled by the condensation of a hexa- and a pentaketide to establish the characteristic central lactone moiety. The projected synthesis of the lactone with the two attached 1,3-diene segments defines one of the central scientific challenges which we hope to resolve relying on a highly modular synthetic strategy. Because the curvicollides A-C are only distinguished by the substituent pattern in the eastern part of the molecule, a successful modular synthesis of curvicollide C should enable the synthesis of the other members of this family of polykketides.

• DFG Programme: Research Grants