Total synthesis of pseudopterosins

• Applicant: Dr. Vincenzo Ramella
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398312835

Studying the biological activities of natural products might lead to new drug candidates. However, having a simple way to generate enough substance and derivatives is often challenging. The research proposed herein aims to develop a concise total synthesis towards all three stereoisomeric pseudopterosin aglycones. Glycosylation of the aglycones gives access to the whole family of pseudopterosins. To date this family of natural products has been of high interest thanks to its various biological activities, including anti-cancer, anti-malarial, antibacterial (Gram-positive) and anti-inflammatory properties. Therefore, a “transformation-based” approach is chosen to enable a compact synthesis. The key step of the planned synthesis includes an oxy-Cope/Michael addition cascade in order to build the tricyclic core in one single step. Late incorporation of the butenyl group gives access to two of three pseudopterosin aglycones using one synthetic route. The third pseudopterosin aglycone can be obtained by starting with the other enantiomer. The planned synthesis reduces the longest-linear sequence to eight steps, gives the fastest access to the desired natural products and offers the opportunity to also synthesize unnatural derivatives.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Christopher Vanderwal, Ph.D.