Microwave-assisted regioselective synthesis of acyclic nucleosides through an alkylating reaction with 2-oxa-1,4-butanediol diacetate

Abstract

An efficient and green procedure for the synthesis of purine acyclic nucleosides through microwave-assisted alkylation of various purine nucleobases with 2-oxa-1,4-butanediol diacetate in the absence of solvent and catalyst is described. The advantages of using this method include its environmental friendliness, simple manipulation, short reaction time, high regioselectivity, and good yields.Key words: acyclic nucleosides, microwave irradiation, regioselectivity, alkylation, 2-oxa-1,4-butanediol diacetate.

Synthesis of Novel C6-Phosphonated Purine Nucleosides under Microwave Irradiation by SNAr−Arbuzov Reaction

“…Herein, during the ongoing course of our study on the development of new methods for the synthesis of nucleoside analogues under microwave irradiation, we applied microwave- assisted SNAr−Arbuzov reaction to the synthesis of a novel series of C6-phosphonated purine nucleosides, which opens a new route for modification at C6 of purine nucleosides.…”

“…At first sight, the C6 chloride atom of 6-chloropurines appears as an inactive and/or unexciting chemical entity for SNAr−Arbuzov reaction compared with commonly used substrates, such as primary alkyl halides or acyl halides. However, from our experience with the facile synthesis of C6-substituted aminopurine analogues under microwave irradiation,14b we knew that the S N Ar reaction of 6-choloropurines could be enhanced by microwave irradiation, so we still envisioned that an SNAr−Arbuzov reaction of 6-halide purines with trialkyl phosphite could be carried out. With this idea in mind, we initiated the study to generate the C6-phosphonated purine under microwave irradiation.…”

“…8.5%) within 20 h at 120 °C (Table , entry 6). Microwave-assisted reaction exhibited several advantages over the conventional heating by not only significantly reducing the reaction time but also by improving the reaction yield dramatically and, in the process, eliminating the side reactions, implying the involvement of a specific nonthermal microwave effect. 14b, …”