Chemoselective Preparation Of1,2,3-triazole Compounds By Tandem Multicomponent Reactions

In past decades, tandem multicomponent reaction is one of the most hot topic in modern organic chemistry. Owing to its atom economy, facile execution, and high efficiency tandem multicomponent reaction has been widely used in combinatorial chemistry, drug discovery and natural products constructure. However, it is difficut for each step to be independent in the tandem process. In this thesis, a chemoselective method has been developed to solve this problem and a series of novel1,2,3-trizole compounds involving in more complex structures were synthesized based on chemoselective tandem multicomponent reactions.As a strating point, alkynyl substituted1,2,3-trizole compounds have been synthesized by chemoselective tandem multicomponent reaction. In this reaction, alkynyl-substituted amines regioselectively reacted with azide and diketene under base condition to provide a monotriazole, leaving the alkynyl group unchanged. There were no Husigen1,3-dipolar cycloaddition products were observed under the optimal condition. The reaction is high efficient and can be used to construct some special bifunctional compounds. For example, bis(1,2,3-triazole)s and1,2,3-triazole-isoxazoles bisfunctional derivatives caan be synthesized by the combination of above three-components reaction with copper-catalyzed "Click" reaction and hypervalent iodine-mediated cycloaddition respectively.Next,1,2,3-trizole-modified peptidomimetics have been synthesized by combination of two different muticonponent reactions. Azide containing bifunctional compounds were selected as "bridge molecular" to combined Ugi four-component reaction with three-component trizole cycloaddition in "one pot". The tandem multicomponent reactions were then utilized with chemoselective reaction to generate alkynyl containing1,2,3--trizole-modified peptidomimetics. In order to verify its possible biological applications, we took advantage of this chemoselective tandem multicomponent reaction to access bis(1,2,3-triazole)-modified peptidomimetics and1,2,3-triazole-isoxazole bisfunctional peptidomimetics. No protecting groups and no separation of intermediate products were required in this protocol.Finally, the chemoselective tandem multicomponent reactions have been applied to construaction of1,2,3-triazole-containing macrocycles by intramolecular Sonogashira cross-couplings. The synthetic protocol embodies a combination of two multicomponent reactions in a one-pot chemoselective fashion followed by intramolecular Pdcatalyzed Sonogashira cross-coupling for ring closing. Three kinds of macrocycles have been successfully synthesized by this method and the diversity can be easily introduced by varying the substitutions on amine, aldehyde, acid and isonitrile. The alkynyl group might have potential synthetic application for further modification.The chemoselective tandem multicomponent reactions were facile execution and high efficiency, which fully lives up to the principle of Green Chemistry"and atom economy. More over, because of cumulative effect, the novel and complex products have potential application in drug discovery. In addition, the increased concentration for the macrocyclization step suggests this process could be a valuable tool for macrocycles synthesis...