Synthesis Of Spirocyclopropyl Oxindole

This thesis is divided into two parts.The first part is the highly diastereoselective synthesis of 3,3'-cyclopropyl spirooxindoles via catalyst-free cyclopropanation using pyridinium N-ylides which will be described in the first and second chapter.The second part is the synthesis of phosphodiesterase inhibitor RPL554 analogues which will be described in the third chapter.The first part is the synthesis 3,3'-cyclopropyl spirooxindoles with the participation of pyridinium N-ylides.Pyridine quaternary ammonium salt is a stable ionic compound.It has active chemical reactivity because of the aromaticity of benzene ring compounds and electron absorption effect of nitrogen atoms.Firstly,we reviewed the application of pyridine quaternary ammonium salt in organic synthesis in chapter 1.In chapter 2,we studied the feasibility of 3,3'-cyclopropyl spirooxindoles synthesized from pyridine quaternary ammonium salts.3,3'-Cyclopropyl spirooxindoles can be efficiently constructed by simple Michael addition-initiated cyclization reaction.with pyridinium N-ylides which was generated from pyridine quaternary ammonium salts in the presence of base.The second part is the synthesis of phosphodiesterase inhibitor RPL554 analogues.RPL554 is a new type of aerosol inhalation PDE3/4 compound inhibitor.By controlling the concentration of PDE3 and PDE 4,we can control inflammation and tracheal expansion in vivo,and then treat chronic obstructive pneumonia.In this chapter,we first explore the synthetic steps of RPL554,and then improve the synthesis methods of different amino substituted analogues.Later,we will test the biological activity of these analogues in order to obtain better therapeutic agents for chronic obstructive pneumonia.