Exploiting activated esters in novel chemoselective amide formation reactions

Abstract

Detailed within this thesis are the synthetic studies performed on the preparation of lipase catalysed activated esters and their subsequent use in the synthesis of pharmaceutically relevant amides. It also includes the application of activated esters in chemoselective amide formation reactions.
The introduction summarizes the significance and use of activating agents in lipase catalysed reactions over the classical methods of amides synthesis. Additionally, a detailed review on some currently available chemoselective N-acylating agents along with their applications is also mentioned. A separate chapter is given to the application of related amides in the designing of biological probes to ultimately detect enzymes which are over-expressed in disease. The discussion begins with the lipase-catalysed synthesis of acetone oxime activated esters and their role in the one-pot synthesis of acetanilides. Further discussion continues with the synthesis of activated esters from ethylene glycol and haloalcohols. The use of a lipase in the synthesis of glycol esters prevented the formation of dimers which indicates its potential usefulness in the future. Unfortunately, these activated esters could not be applied to a synthesis of amides in the same manner as acetone oxime. Thereafter the section focuses on the investigation and synthesis a novel chemoselective N-acylating agent and its subsequent applications in the synthesis of pharmaceutically important amides, in particular, those involving chemoselective reactions between anilines and N-substituted anilines. Additionally, the chemoselective agent was also used in preparation of pharmaceutically important compounds. To round off the thesis the application of one of the target compounds-benzanilide-was used to develop and synthesise a novel biological probe and to scope out its potential for application in the detection of enzyme-controlled disease. The preliminary utility of the probe was demonstrated using HPLC and NMR.
The thesis concludes with the experimental encompassing experimental details, spectroscopic and analytical analysis of all the compounds described.