Bioactive molecules against proteasome and cysteine proteases. Synthetic approach to vicinal diamines

Abstract

This PhD thesis presents research advancements in the fields of organic synthesis and medicinal chemistry. The work is structured into three chapters, each focusing on distinct topics. The first chapter explores the synthesis of 1,2-diamines derived from aldehydes. This involves a three-step telescoped process, starting with a Darzens reaction to produce intermediate epoxysulfones. These intermediates react with amines to form amino-imines, which are subsequently converted into the final diamines using a reductive agent. The remaining two chapters focus on the design, synthesis, and evaluation of protease inhibitors. The second chapter details the development of novel proteasome inhibitors, designed as enhancements to well-known proteasome inhibitors, exhibiting in vitro activity in the nanomolar range. The third chapter describes the serendipitous discovery and preparation of a new class of compounds containing a carbamoyl azide functional group as a reactive warhead. These peptidyl carbamoyl azides have been identified as potent inhibitors of cysteine proteases.