Stereoselektive Cascade Aldol Reactions for Expeditious. Total Synthesis of Polyketide Natural Products

• Applicant: Dr. Jakub Saadi
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169599524

A novel approach to polyketide synthesis via one-pot, cascade Mukaiyama cross-aldol reactions of super-silyl enol ethers is pioneered since 2006 by the group of Professor Yamamoto and allows for a remarkably efficacious, stereoselective and instant access to a highly bioactive and pharmaceutically relevant class of natural products. This powerful approach combines multiple steps in a single reaction, yielding complex products without the need of isolation of intermediates or lengthy protective group manipulations. Further exploration of this exceptional new method is therefore of the highest interest for progression of pharmaceutical sciences and for both economical and ecological reasons. This project aims at development and application of this process to a concise, expeditious synthesis of bioactive natural products. First, reaction conditions will be optimized to smoothly promote multiple (≥3) cascade aldol reactions in one pot. In parallel, crossaldehyde coupling reactions leading to highly substituted polyhydroxylated aldehydes will be studied. Next, coupling of aldehyde fragments to 3-oxo-1,5-diols will be performed. Finally, new developments will be applied to the synthesis of natural products of the Polymethoxydiene type and of a polyketide fragment of the Aflastatin A.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Hisashi Yamamoto, Ph.D.