The Catalytic, Asymmetric Interrupted Feist-Benary Reaction

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DESCRIPTION (provided by applicant): Project Summary: Most of the drugs used to treat the diseases plaguing mankind are made, or synthesized, by humans, rather than being isolated from natural source. Therefore, it is very important to keep developing new reactions for synthesizing "drug-like" molecules, likely to have beneficial activity. This proposal describes an investigation of one particular reaction, the "interrupted" Feist-Benary (IFB) reaction. This reaction generates a specific molecular structure present in a number of molecules that have the potential to treat such conditions as fungal, bacterial and viral infections, along with some forms of cancer. Furthermore, the IFB reaction controls the chirality of this molecular structure. Chirality is a property associated with the three-dimensional shape of a molecule and is fundamental in determining how a molecule interacts with a biological system. It is also particularly difficult to control the chirality of a product, but the IFB reaction very effectively does this for the creation of the drug-like molecular structure. The proposal describes plans for understanding how the IFB reaction controls the chirality of the product, for testing how wide a variety of products the reaction can produce, and for using the reaction in the synthesis of three families of biologically active, potentially clinically active molecules. Relevance: This proposal describes the synthesis of several families of potential antifungal, antibiotic, antiviral, and anticancer agents. It is essential to develop new agents with all these activities, as fungi, bacteria and viruses are all developing resistance to existing drugs, and the existing anticancer agents have limited activity and potent side-effects.