Synthese van 1,2,3-triazolen en biologische evaluatie

摘要

Over the past decade, organocatalytic synthetic procedures have emerged as an essential part of triazole chemistry. In order to avoid various obstacles of metal catalyzed synthesis of triazole in biological systems, various organocatalyzed syntheses were developed.This thesis is dedicated to the exploration of various triazolization strategies towards functionalized 1,2,3-triazole moieties and studies of their activities against cancer as well as viral cell lines. These triazolization strategies rely on inexpensive and readily available starting materials. In chapter 1 a brief summary of previously discovered organocatalyzed methodologies towards functionalized 1,2,3-triazoles as well as their biological study and the synthesis of biological active molecules containing triazole as a core unit have been presented concisely. The goals and objectives of this thesis are also elaborated in this chapter. Chapter 2 describes a three-component reaction of readily available starting materials such as enolizable ketones, primary amines, and para-nitrophenyl azide leading to trisubstituted triazoles. This newly developed methodology has been used to functionalize various natural compounds and to synthesize various multifunctional building blocks. Chapter 3 is dedicated to the formation of NH-1,2,3-triazoles from readily available starting materials such as enolizable ketones, ammonium acetate, and para-nitro phenyl azide. The utility of the reaction has further dmonstrated by direct conversion of compounds containing enolizable keto groups to the corresponding triazole heterocycles. Chapter 4 elucidates a highly efficient and regiospecific Zn(OAc)2-mediated synthesis of propargyl functionalized triazole derivatives in a single step from ketones and propargyl amine. This methodology has given access to a special type of triazoles which are not possible to synthesize by other means. Furthermore, we have discussed the functionalization of propargyl triazoles with azides via click reaction to form an unique type of N-C linked bis-triazoles. Chapter 5 represents an unprecedented selective decomposition of bis(1,2,3-triazoles) by a Rh(II)-catalyzed [3 + 2]-intramolecular annulation reaction which leads to the formation of 3,4-fused indoles. Extension of this protocol to heterocycles lead to interesting polyfused 1,2,3-triazole derivatives. In chapter 6 a series of newly functionalized artemisinin derivatives have been prepared using an organocatalytic multicomponent reaction in order to study their activity in viral cell lines. Chapter 7 deals with the development of three synthetic strategies to access 1,4-disubstituted, 1,5-disubstituted, and fused 1,2,3-triazoles analogues of artemisinin with promising anticancer activity.