Grant: Research Tools and Instruments - Category 1 (<$150,000)

The proposed research has as its overarching aim the provision of synthetic solutions to problems of molecular complexity by developing new reactions using molecular rearrangements as key design elements.  The approach to these problems will be twofold:  i) we will target complex natural products with important biological properties, and ii) we will develop new complexity generating reactions that should be widely useful to the synthetic community.Specifically, we will develop a synthesis of cortistatin A, an important natural product and potential lead for the development of anticancer-therapeutics.  To carry out this synthesis, a new cascade reaction has been designed to deal with some of the central structural issues present in the target compound.  Successful completion of this work will allow biological evaluation for anti-angiogenic activity (in collaboration with Professor Tara Haas of York University).In addition, we are interested in developing complexity-generating reactions using sequential molecular rearrangements.  These reactions are expected to have wide application by the community since they provide access to enantioenriched polysubstituted chiral carbocyclic, heterocyclic and acyclic compounds.Crucial to our work is the rapid analysis of multiple reactions in support of optimization.  HPLC analysis has supplanted other more time-consuming and less accurate techniques as the standard method of analysis.  The HPLC station requested will have a significant impact on the success of our reasearch.