Development of the First Ruthenium-Iminium-SOMO Organocatalytic Cascade and Its Application in Total Synthesis of the Highly Bioactive Natural Products Viroallosecurinine and Norsecurinine

• Applicant: Dr. Dominik Hager
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 238839157

Organocatalysis has become a tremendously important field of organic chemistry over the past decades. Small molecules can catalyze a variety of different transformations in an asymmetric manner, paving the way to hitherto unknown scaffolds. The most common organocatalytic reactions utilize aldehydes as substrates, and are distinguished by one of three major activation modes of aldehydes, namely iminium, enamine, and SOMO (single occupied molecular orbital) activation. Each mode per se is a powerful tool to generate chiral synthons, but the merger of two or more organocatalytic modes to cascade reactions enables the rapid conversion of simple achiral staring materials into stereochemically complex, enantiomerically pure products. These compounds serve as versatile intermediates en route to structurally diverse natural products and drug-like molecules. Thus, the concept of organocascade catalysis is a powerful tool for natural product synthesis, able to imitate Nature's efficient biosynthetic pathways. The research described in this proposal represents a challenging enterprise for the development of the first ruthenium-iminium-SOMO organocatalytic cascade, and its application in the efficient synthesis of highly bioactive natural products of the Securinega class. In the methodology development phase of this project, the viability of three different catalytic cycles will have to be established independently. Then, the three catalytic cycles will be merged to an organocascade transformation. Finally, the short synthesis of the bactericides viroallosecurinine and norsecurinine will be completed in just nine synthetic steps from commercially available starting material.Given the antibacterial properties of viroallosecurinine, the results of this work will be particularly relevant for drug discovery and development within the pharmaceutical industry. In addition, this research will impact significantly on the growing field of organocatalysis, and inspire the discovery of new types of reactivity, novel modes of activation and the marriage of these new reactivities for the discovery of unprecedented cascade processes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor David W. C. MacMillan, Ph.D.