Disulfides For Multicomponent Reactions With Isocyanides And A Broad Range Of Nucleophiles

Sulfur-containing compounds are numerous and widely used,they play an important role in natural compounds,important bioactive molecules and various functional materials.When referring to preparation,effective activation is the key to synthesis novel sulfur-containing compounds.The isothioureas and their derivatives involved in this thesis can be used as core pharmacophores of various drug molecules(such as anion exchange transporter 1 inhibitor: uric acid,receptor antagonist,CXCR 4)and other small organic molecules catalysts.Nowadays,the methods for constructing new sulfur-containing compounds have certain limitations,such as complicated synthesis steps,high cost,and environmental pollution.Therefore,it is undoubtedly an important goal to construct isothioureas through a more cost-effective and green synthetic pathway.We employed the synthesis path of activated disulfide compounds with isocyanides and different nucleophiles through a one-pot process to construct a variety of isothioureas and useful molecules.This proposal has advantages such as mild reaction conditional and simplified operational procedures.The main method of this thesis is based on the low-cost and easily available disulfide compounds.Under the initiation of TEMPO,the sulfur halide and sulfur nitrogen formed by the activation of NXS,then react with isocyanides and various nucleophile(N,O,S,C)to form the isothiourea compounds.The mainly research work involved in this thesis can possess the following three characteristics:1.During the secondary nucleophilic reaction,the formed carbon-positive intermediate can be reacted with various nucleophiles to construct a new sulfur-containing compound.These nucleophiles include: N,O,S,C,etc.,and the nitrogen-containing nucleophiles are: hydrazine,aromatic amine,primary fatty amine,secondary fatty amine,ammonia,and so on.2.The study involved the construction of five-and six-membered heterocyclic compounds with N,S,which provide a new method for the synthesis of heterocyclic compounds of the type.And the chiral test result showed that our method can effectively maintain the configuration of the chiral center.3.In terms of new drug synthesis,we have successfully constructed anti-gout drug,Lesinurad,through greatly simplified steps.This method increased the overall reaction yield(36%)and is environmental friendly compared with the existing reports.