Studies On The Synthesis Of C-6-Modified Purine Nucleosides By Chiral Amino Acid And Its Derivatives

Nucleosides play important roles in many biological processes. Many nucleoside analogues withmodifications on the heterocyclic bases have been investigated for their antiviral and anticancer activivities.Recently, there are extensive interests in the study of purine derivatives with various substituents at6due totheir broad spectrum of biological activities. Nevertheless, there are some insufficiencies, which still cannot be avoided, such as: the high cost of synthesis, weak performance, short duration, toxic side effects andso on.Therefore, the development of efficient low-cost and low toxicity nucleoside drugs are still themajority challenges for the chemical and pharmaceutical scientists.The naturally occurring N-(purin-6-yl)amino acids play important roles in many biological processes.While N-(Purin-6-yl)-amino-alcohol also attracts attention of people as there unique bioactivities. Provingthe big rile of slective adenosine reseptor compound, Pier Giovanni Baraldi reported a new2-Heterocyclyl-imidazo[2,1-i]purin-5-one derivatives as potent and slective human A3adenosine receptorantagonists in April2011. Actually, early in1991Norton P. Peet et al. had applied for patent rights of theseadenosine receptor compounds. However, there are few reports on the synthesis of N-(purin-6-yl)aminoacids, also, there is no detailed study on such compounds. Just imagine, a route with simple produre andsaving and raw materials in big scaled producing, most importantly, which is able to stop abruptly to givedesired product is urgently needed. Based on our former work on the synthesis of various nucleosideanalogues, a bright new route with green solvent and one-pot several steps to synthesis series ofN-(Purin-6-yl)-amino-acid attracts our interests.We have developed a novel and efficient synthetic route to N-(Purin-6-yl)-amino acids andN-(Purin-6-yl)-amino-acid ester as well as adenosine reseptor compound derivatives only have to increasethe equivalence of TEA in step2. This method represents an alternative and simple method to solveproblems in reactions with amino acids. One pot reaction with shorter reaction times and higher yields witheasier post treatment were achieved for the large scale production. Compared to previously knownapproaches, the simplicity of this procedure and generally excellent yields make this method a particularlyvaluable one. Meanwhile, we also studied synthesis of series of9-imine purine derivatives. After a large number ofconditions screened, we found a way which starts with oximes.Using DCM as solvent, under N2protecting,we get a series of9-imine purine derivatives in one-pot route. Further studies are still beingreacted, aiming to get9-(4,5-dihydro-3H-pyrrol-2-yl)-9H-purine derivatives.Their structures were confirmed by1H NMR,13C NMR,31P NMR, IR and HRMS.We report that this opens an effective new avenue for modification at purine nucleosides, and theseresults have good value in academy and application.