Microwave-assisted The Rapid And Green Synthesis Of Nucleosides And Their Derivatives

Recently, the research on the antibacterial, antiviral and antitumor drugs is a hot topic in the pharmaceutical chemistry. In this paper, we have devoted our efforts to design and prepare acyclic nucleosides, 8-bromo adenosine derivatives and 5-iodo uracil derivatives. It is the first time that we introduce water as the solvent to synthesize acyclic and halo atom substituted nucleosides with the help of microwave irradiation and several innovative results have been obtained.60 acyclic nucleoside derivatives were achieved in high yields and good regioselectivity, under microwave irradiation via Michael addition of various nucleobases toα,β-unsaturated methylene compounds, using water as the solvent and TEA as the base, 27 of which are new ones. Another 33 acyclic nucleosides, which can be used as important building blocks for peptide nucleic acids (PNAs), were obtained in water and DMF through the nucleophilic substitution of various nucleobases with chloroacetate, assisted by microwave irradiation, of which 16 compounds have not been reported in literatures. Six 8-bromo adenosine derivatives and six 5-iodo uracil derivatives were finished in aqueous system within short reaction times. Their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and/or elemental analysis, and some of them were further ascertained by HMQC and HMBC spectra in order to assert the site of alkylation. We have systemically studied the methodology of microwave-promoted the preparation of nucleosides, obtained the optimal reaction conditions, and realized the rapid and green synthesis of this kinds of compounds.In this paper, a number of nucleoside derivatives were synthesized under microwave irradiation using water as the green solvent, which testified that our design on the green synthesis of nucleosides is rational, which presents an important model for the preparation of these kinds of compounds in other environmental-friendly systems, such as room temperature ionic liquids, super-critical CO2. In summary, we get through the green route of microwave-assisted the rapid syntheses of nucleosides and their derivatives in water and these results have good value in learning and application.