Total Synthesis of Rameswaralide

• Applicant: Dr. Daniel Zell
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398264478

This research project is focused on the synthesis of the natural product Rameswaralide, which belongs to the widely occurring natural product class of cembranoids. It has shown to exhibit particularly effective anti-inflammatory effects against inter alia arthritis and psoriasis. Despite undisputed advances to construct key structural motifs of Rameswaralide, its total synthesis has so far proved elusive and its absolute configuration still remains unknown. This research project is directed towards the atom- and step-economical total synthesis of Rameswaralide starting from the naturally abundant starting material β-pinene. In order to ensure an overall low number of steps in the total synthesis, a particular focus is put on minimizing the use of protecting groups. Thus, the research project is intended to be conducted in the group of Prof. Dr. Dr. h.c. mult. Barry M. Trost, who is internationally highly renowned for his approach of atom economy in organic synthesis.The major aim of a stereoselective total synthesis is to determine the absolute configuration of the naturally occurring enantiomer of Rameswaralide. Additionally, the planned synthesis should pave the way to a fully stereocomplementary approach leading to the other enantiomer. In this way, the unnatural enantiomer can be synthesized either way. Since enantioselectivity can have a major impact on the bioactivity of a molecule, a study of its biological activity could be of high relevance to pharmaceutical chemistry. Based on the preliminary work, including the approach of the Trost group to partially synthesize Rameswaralide, a new retrosynthetic analysis of the target molecule should circumvent the use of so far unsuccessful reactions. In contrast, ecologically and economically sound catalytic processes are considered as key reactions to access the target molecule in the overall lowest possible number of steps. This approach could possibly include the modification of existing reactions or the design of new catalytic processes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Barry M. Trost