The Nucleobase-Modified Protocal For The Synthesis Of Nucleoside Analogues Under Microwave Irradiation

Recently, the research on the antibacterial, antiviral and antitumor nucleosides is a hot topic in the pharmaceutical chemistry. In this paper, we have devoted our efforts to design and synthesis the novel nucleosides, and employ water as the solvent for the synthesis nucleoside derivatives, based on the modification of nucleobase. The synthesis of nucleosides under microwave irradiation was reviewed throughly, especilly in the green synthesis. It is the first time that we introduce phosphonate functional group into purine moiety, through the first reported Arbuzov reaction bettween 6-chloropurines and trialkyl phosphonite. Using water as the solvent, we facilitated the classical metheods to synthesis nucleoside derivatives with the help of microwave irradiation, and several innovative results have been obtained.A seriers of C6-phosphonated purine nucleosides were obtained in good to excellent isolated yields by the simple and catalyst-free Arbuzov-type reaction of trialkyl phosphite with 6-choloropurine nucleosides, including a series of non-sugar carbon nucleosides. All the products were reported firstly. And these products can be applied to develop biologically active compounds. The pharmacological evaluation of these compounds are undergoing in our laboratories. This not only broaden the scopes of modified nucleosides, but also advance our understanding about C6-substituted purine nucleosides.Using water as the solvent, we facilitated the classical metheods to synthesis nucleoside derivatives with the help of microwave irradiation. 33 unsatruted nucleosides were synthsised through the N-alkylation, including 16 novel products. 10 8-substituted purine nucleosides were synthesized through substitution of 8-bromo purine nucleosides. We developed two protocols to synthesis 5-iodo uracil derivertives in aqueous mediea. We have systemically studied the methodology of microwave-promoted preparation of nucleosides, obtained the optimal reaction conditions, and realized the rapid and green synthesis of this kinds of compounds.Their structures were confirmed by ¹H-NMR, ¹³C-NMR, ³¹P-NMR, HRMS and/or elemental analysis, and some of them were further ascertained by X-single crystal.We report that this opens an effective new avenue for modification at C6 of purine nucleosides, and realize the rapid syntheses of nucleosides and their derivatives in water. These results have good value in academic field and application.