Study On Chiral Cyclic Nucleosid Analogues Via Palladium(0)-catalyzed [3+2] Cycloaddition Of Vinylcyclopropanes And α-nucleobase Substituted Acrylates

Carbocyclic nucleosides compounds have already become the focus because of its anti-tumor and anti-viral activity in recent years, so their synthesis and research play an important role in medicinal chemistry. While the synthesis of carbocyclic nucleosides are the most challenging in nucleosides. The traditional synthesis of carbocyclic nucleoside focused on the introduction of one chiral carbocyclic to the purine or pyrimidine base at present. Whereas it is difficult for the synthesis of chiral carbon-ring, mainly reflects in requiring to design some reactions carefully in order to introduce some chiral. The synthetic steps is long result to the low yield in the end. With the rapid development of new nucleoside drugs of the international research and production, the demand for chiral cyclicnucleoside of potentially antiviral activity is growing. So how can the medicinal and chemistry researcher to study synthesis of chiral cyclicnucleoside efficient has become the top priority, it is one of the problems which need to be solved.This paper based on the concept of “Diastereoselective synthesis of chiral cyclic nucleoside analogues via palladium(0)-catalyzed asymmetric [3+2] cycloaddition”. A variety of cyclopentane nucleoside compounds were synthesized via the method of asymmetric catalytic of purine, pyrimidine and heterocyclic base to cheap vinyl cyclopropane in the present of palladium(0) and chiral ligands.We synthesized several kinds of chiral ligands, for the first time to achieve a series of cyclopentane nucleoside compounds of α-purine, pyrimidine or heterocyclic base substituted with acrylates vinyl cyclopropane in the present of Pd2dba3 and chiral ligands L7 by [3+2] cycloaddition, it can up to 99% yield and 92% ee. The achieved chiral cyclopentane nucleoside can be subjected to further extension to get some chiral drug analogs by reducing the ester group to hydroxyl group. In the experiments we found that the solvent in the reaction system has a certain influence for the ee. The rate is soon and start materials can be fineshed in one hours. This method of synthesizing cyclopentane nucleoside not only increases the carbocyclic nucleoside compounds but also overcomes the disadvantages of low yield and more steps.In this pater, we obtained the optimal conditions by screening a variety of conditions. With it in hand, we got 47 new chiral cyclopentane nucleoside by the α- bases acrylate of the different partsofmodifiedwithvariousvinylcyclopropane.wecultiveasinglecrystalanddeterminetheabsoluteconfigurationbycrystaldiffractionexperiment.theresultingstructureofthecompoundshasbeencharacterizedby1 hnmr,13cnmrandhrms.