[Au]/[Ag] Catalyzed Synthesis of Benzyl Ethers, N-glycosides and Molnupiravir

Abstract

Carbohydrates are one of the four significant biomolecules present in nature that acts primarily as a major source of energy for living organisms. Apart from this, carbohydrate molecules enormously impact many biological phenomena such as cell growth, cell-cell recognition, fertilization, immune response, viral replications, and so on. Unlike protein and nucleic acids, isolating carbohydrates in their homogeneous form from natural sources is extremely difficult as glycans and glycoconjugates commonly exist as microheterogeneous mixtures with a high density of hydroxyl groups. The difficulties associated with the isolation process give rise to openings for chemical synthesis as pure structures can be obtained by chemical methods, which are necessary to understand the role of glycans in living organisms. Chemical glycosylation methods shall comprise a careful protection-deprotection strategy of hydroxyl groups to avoid the formation of undesired products. In this context, in 2016, Mishra et al. reported a stable alkynyl glycosyl carbonate donor, which has enormous potential to become a universal glycosyl donor. The submitted thesis consists of four chapters that focus on the development of novel methods for synthesizing important glycosides. Chapter 1 depicts a brief overview of existing glycosylation methods and the importance of glycoconjugates in therapeutics. In chapter 2, a novel method developed for etherification that solves a current major issue in synthetic carbohydrate chemistry by exploiting salient features of ethynyl cyclohexyl moiety and [Au/Ag] catalyst is discussed. Chapter 3 focuses on developing new methods for synthesizing various challenging N-glycosides and modified nucleosides that are otherwise difficult to prepare. Discussion on a newly discovered route for the shortest chemical route established for synthesizing the antiviral drug Molnupiravir (EIDD-2801) will be found in chapter 4.