A Straightforward Entry To Chiral Cyclopropyl Carbocyclic Purine Nuleosides Via Ruthenium(Ⅱ)-catalyzed Asymmetric Intramoclecular Cyclopropanations

Nucleosides compounds have always drawn the focus of people because of its anti-tumor and anti-viral activity.The classic synthesis of nucleoside componds is so difficult that we urgently need to find a new synthesis method to construct chiral nucleoside.Among the numerous nucleoside compounds,chiral carbocyclic nucleoside takes up a large proportion of these compounds.Hence,how to efficiently synthesis of chiral nucleoside compounds is a problem urgently to be solved.Since no ring guanosine ACV was found,chemists have designed and synthesized nucloside compounds of similar structures including chiral cyclopropyl carbocyclic nucleosides.The development of new chiral carbocyclic nucleoside methods and rich of nucloside compounds drug screening of molecular libralies have became an urgent problem which the drug and chemical workers need to be considered.This paper based on the strategy of “A Straightforward Entry to Chiral Cyclopropyl Carbocyclic Nucleoside Analogues via Enantioselective Intramolecular Cyclopropanation Reactions”.A variety of intermolecular purine-derived diazoacetates have been synthesized and the desired cyclopropyl carbocyclic nucleoside analogues were obtained under Ru(II).Our research group have devoted to the modification of nucleoside bases all the time.In this paper,on the basis of our group previous work,we designed and synthesized intramolecular purine-derived diazoacetate for the first time.Through the screening of different metals,catalysts,solvents and temperatures,we reported an enantioselective synthesis of cyclopropyl carbocyclic nucleoside analogues via asymmetric intramolecular cyclopropanation reactions.It should be noted that the corresponding cyclopropyl purine nucleoside analogue has three continuous stereocenters and a [3.1.0] bicyclo skeleton,delivering the desired cyclopropyl carbocyclic nucleoside analogues up to 99% yields,99% ee.Chiral cyclopropyl carbocyclic nucleoside analogues with quaternary stereocenters were achieved in moderate yields and enantioselectives.To evaluate the potential of the intramolecular cyclopropanation products,additional transformations were performed.The products obtained could undergo diverse transformations including an easy access to chiral cyclopropyl adenosine nucleoside which exhibits anti-BLV activity.The experiment has many advantages such as short reaction time,simple operation,mild condition,high yield,and good enantioselectives.New method has more application value than traditional synthesis method,and more advantages in rich chiral ternary carbocyclic nucleoside compounds drug screening of molecular libraries.In this paper,we have reported a straightforward entry to chiral cyclopropyl carbocyclic nucleoside analogues via the highly enantioselective intramolecular cyclopropanation reactions for the first time.All the resulting structure of the compounds have been characterized by 1H NMR,13 C NMR.The absolute configuration of chiral cyclopropyl carbocyclic nucleoside was determined by the single-crystal X-ray diffraction analysis.