Synthetic Studies on (E)-Alkene Peptide Isosteres and Thiophene-containing Furanosteroids

摘要: Peptide isosteres are important tools for the understanding of peptide function and development drugs. (E)-Alkene particularly useful due to their close geometric match amide bond structure. We developed a method generation small library (E)-alkene on solid support via cuprate mediated SN2′ ring opening allylic BUS-aziridines. also studied selectivity these aziridines in solution phase.Halenaquinone is marine natural product that was first isolated 1983 from Pacific sponge Xestosongia exigua. realized synthesis thiophene-containing analog, thio-halenaquinone. The key steps include an alkynyl ketone-benzocylcobutane Diels-Alder reaction construct naphthalene subunit, Heck cyclization form quaternary carbon, closing metathesis install final ring. This compound showed IC90 ~5 µM against Pfnek-1 analog had ~3 µM. Based results we designed synthesized simplified ~4 selected move animal testing optimized preparation 200 mg lead