Enantioselective synthesis of bioactive molecules and development of synthetic methodologies involving formation of quinoline and coumarin derivatives via Rh-catalyzed ortho C-H bond activation of aromatics

Abstract

Enantioselective Synthesis of Bioactive Molecules and Development of Synthetic Methodologies Involving Formation of Quinoline and Coumarin Derivatives via Rh-Catalyzed ortho C-H Bond Activation of Aromatics Research Student: Sunita K. Gadakh AcSIR Roll: 10CC11J26017 Research Guide: Dr. A. Sudalai The thesis entitled “Enantioselective Synthesis of Bioactive Molecules and Development of Synthetic Methodologies Involving Formation of Quinoline and Coumarin Derivatives via Rh-Catalyzed ortho C-H Bond Activation of Aromatics’’ is divided into four chapters. The title of the thesis clearly reflects the objective, which is to synthesize the bioactive molecules and utilizes the Rh catalysis for the development of synthetic methodologies applied to the synthesis of bioactive molecules and their intermediates. Chapter I deals with the synthesis of HIV protease inhibitor amprenavir, saquinavir, nelfinavir and its analogue via Co-catalyzed hydrolytic kinetic resolution (HKR) of racemic anti-azido epoxides with two consecutive stereocentres to generate the corresponding diols and epoxides in high enantiomeric purity (97–99% ee) in a single step. Chapter II describes the synthesis of other important molecules like yashabushidiols A and B and lactone unit of compactin and mevinolin by employing same chiral inducing step (i.e. Co-catalyzed two stereocentred HKR of β–hydroxy epoxide). Also, in this chapter we have presented the enantioselective synthesis of anti-Helicobacter agent (+)-spirolaxine methyl ether using brown allylation and noyori’s asymmetric reduction strategy. Chapter III deals with a simple and efficient synthesis of isocoumarins and alkylidenephthalides from 3-(1-hydroxycarbethoxy/alkyl)phthalides with DEAD/PPh3 and catalytic amount of TBHP system. Its application is demonstrated in the total synthesis of bioactive molecules such as cytogenin and (Z)-3-butylidene-7-hydroxy-5-methoxyphthalide. Chapter IV describes Rh-catalyzed regioselective oxidative cyclization of aromatic anilines with alkyl propiolates for the synthesis of quinoline carboxylates and its application in the synthesis of quinolone antibiotic oxolinic acid. Also, in this chapter, we have utilized same catalytic system for the synthesis of bioactive coumarin derivatives in high yields.