@unpublished{pittir8450,
           month = {November},
           title = {Synthetic Studies on (E)-Alkene Peptide Isosteres and Thiophene-containing Furanosteroids},
          author = {Bryan Wakefield},
            year = {2008},
        keywords = {halenaquinone; peptide isosteres; thio-halenaquinone},
             url = {http://d-scholarship-dev.library.pitt.edu/8450/},
        abstract = {Peptide isosteres are important tools for the understanding of peptide function and for the development of drugs. (E)-Alkene peptide isosteres are particularly useful due to their close geometric match of the amide bond structure. We developed a method for the generation of a small library of (E)-alkene peptide isosteres on solid support via cuprate mediated SN2? ring opening of allylic BUS-aziridines. We also studied the selectivity for the opening of these aziridines in the solution phase.Halenaquinone is a marine natural product that was first isolated in 1983 from the Pacific sponge Xestosongia exigua. We realized the synthesis of a thiophene-containing analog, thio-halenaquinone. The key steps include an alkynyl ketone-benzocylcobutane Diels-Alder reaction to construct the naphthalene subunit, a Heck cyclization to form the quaternary carbon, and a ring closing metathesis to install the final ring. This compound showed an IC90 {\texttt{\char126}}5 ?M against Pfnek-1 and an analog that had an IC90 {\texttt{\char126}}3 ?M. Based on these results we designed and synthesized a simplified analog that showed an IC90 {\texttt{\char126}}4 ?M. This compound was selected to move on to animal testing and the synthesis was optimized for the preparation of and 200 mg of the lead structure.}
}