Copper-catalyzed C-H Bond Oxidation Of Purine C~8Position: One Pot Synthesis Of7,9-Dialkyl-Purine-8-Ones

The compounds of modified purine base and its analogues such as benzimidazole haveimportant applications in biology and medicine, and are recognized as a class of drugs which havemost potential antiviral activity, so the modification of purine compounds and its analogues hasbecame a hot research for scientists to synthesize these compounds. Nucleoside compounds playan important role in the treatment of disease and physiological, particularly, purine-8-onecompounds have an important biological significance in DNA replication, cancer and ageing. It isreported that patients with leukemia excrete higher levels of8-oxoguanine in urine than normalhumans, and also reported that alkyl substituted8-oxoadenosine has important biological activityand huge application in drugs and pathological aspects.So far, the methods of the synthesis of purine-8-ones are mainly the following three：first, theoxidation of purine which has a heteroatom at C-8position; second, metal-catalyzed cyclizationreaction; third, the oxidation of purine quaternary ammonium salts. Most of the methods abovementioned has certain limitations, for example, more reaction steps, the lower yields, theextensibility of the substrates is not high, post-processing is complex and so on. Therefore, todevelop a new method for synthetic purin-8-ones compounds has a good methodologiessignificance.We firstly reported the method of one pot synthesis of the7,9-dialkyl-purine-8-ones throughcopper catalyzed C-H bond oxidation which reduced the reaction steps, improved the proudctyield and greatly expanded range of sbustrates. We provided a new idea for the modification ofpurine-base compound, and most of the compound synthesized was a new compound, enriched thetype of purine nuclesoside compound. We also applied the reaction system to a benzimidazoletype compound and also received a good effect, synthesized a series of1,3-dialkyl-benzimidazole-2-ones. The reaction system had a good response to the applicability,and provided a new route for the synthesis of disubstituted ureas and had broad applicationprospects.The structures of all the target compounds reported in this paper are characterized by1HNMR,13C NMR, HRMS, and the results are entirely correct, some of the compounds cultivate a single crystal and crystal diffraction experiments further confirmed the structure of the targetcompounds.We developed a new method for the modification of purine base and its analogues, whichhad a very important significance and application value.