This project focuses on the development and application of carbon carbon bond cleavage reactions for the synthesis of complex molecular structures. While much effort in organic synthesis is pointed toward making new bonds, the ability to break specific bonds as needed can greatly simplify synthetic challenges. The proposed reactions of heterocyclic vinylogous acyl triflates (VATs) create a unique, general strategy for the synthesis of acyl-protected homopropargyl alcohols and amines, which can be difficult to prepare by other means. The proposed total synthesis of palmerolide A takes advantage of the chiral homopropargyl alcohols that can be made available by this methodology.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Gregory B. Dudley of the Department of Chemistry and Biochemistry at Florida State University. Professor Dudley's research efforts revolve around the development of new strategies for organic synthesis, with an emphasis on bond-cleaving fragmentation methods. Successful development of the methodology will impact chemical synthesis, especially as it pertains to the pharmaceutical industry.
Synthetic chemists rightfully focus on bond-forming reactions for the construction of complex molecules. However, innovative applications of bond-cleavage reactions can provide access to valuable chemical targets that are otherwise difficult to prepare. This methodology project is focused on the development of bond-cleavage reactions for chemical synthesis. Specifically, new fragmentation reactions have been developed, in which readily available ring structures are broken down to provide valuable open-chain alkyne (acetylene) building blocks. These alkynes are valuable starting materials for synthetic chemistry, so this research impacts diverse research interests in chemistry and related sciences. In addition to developing several aspects of this new bond-cleaving methodology, applications to the synthesis of complex molecular targets, most notably the potential anti-melanoma compound palmerolide A, have been developed. Towards the end of the funding period, the core ring fragmentation methodology evolved into a new direction: ring expansion methodology. The preparation of closed-chain (cyclic) alkynes is highly significant, because these cyclic alkynes can be used in "click" coupling reactions in biological systems. Organic reactions that can be performed in living systems (bioorthogonal chemistry) is a significant new direction for research in the molecular sciences, and the ring expansion methodology can provide new tools for these efforts. This fundamental methodology research will support new developments in diverse areas of the molecular sciences, including chemical synthesis, molecular biology, and nanomaterials science.
