This project is focused on the development of novel rearrangement reactions and their application to complex targets of biomedical interest. Two key rearrangement reactions, the allylic diazene rearrangement (stereoselective C-H bond formation) and the Ireland-Claisen rearrangement (stereoselective C-C bond formation) will be studied. A new acyclic variant of the allylic diazene rearrangement could enable 1,4-stereocontrol between alkoxy and alkyl bearing stereocenters, while a new variant of the Ireland-Claisen rearrangement will extend the scope of this widely used transformation to sterically congested bis-allylic esters. Once the two rearrangement reactions are optimized, they will be applied to the total synthesis of FKBP-12 binding agent, Antascomicin B. The planned synthesis involves four rearrangement sequences to install 6 of the 12 stereocenters in Antascomicin B.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Matthias C. McIntosh, of the Department of Chemistry and Biochemistry at University of Arkansas. Professor McIntosh and his students will be investigating important rearrangement reactions for the synthesis of complex molecules of biological relevance. Rearrangement reactions can simplify greatly the synthesis of complex organic molecules, which need to be prepared in large numbers in the development of new and efficient medicines.
