Synthesis Of New Multisubstituted Isoquinolinones By Ugi Reaction

Multisubstituted isoquinolinones are an important heterocyclic scaffold for many naturally occurring products, which have been found to show widespread biological activities. For example, A wide variety of derivatives of isoquinolinone have been used as Urokinase-Type Plasminogen Activator inhibitors, PARP inhibitors, antimicrobial inhibitors, antitumors agents,5-HT3receptor antagonists, AT1receptor antagonists. It is this wide range of biological and pharmacological importance of isoquinolinones that promoted us to prepare new derivatives of these compounds, utilizing a simple and efficient method. In this dissertation, we studied synthesis of new isoquinolinone by Ugi reaction.The cyclization conditions and the spectral properties were also studied, it can be summarized as following:1.2,3-disubstituted isoquinolin-1(2H)-one were prepared by a sequential Ugi4cc/Wittig reaction, starting from phosphonium salt3, aldehyde, secondary amine, and isocyanide.2. The α-acylamino amide compounds6, obtained from the Ugi reaction of methyl2-formylbenzoate, primary amine, and isocyanide, were transferred intol,2,3,4-tetrahydroisoquinolin-1,3-dione7by the the intramolecular nucleophilic substitution reaction under basic condition.