Microwave-Assisted Rapid Synthesis of 2,6,9-Substituted Purines

摘要

Purine analogues represent an excellent scaffold for targeting many biosynthetic, regulatory, and signal transduction proteins including cellular kinases, G proteins, and polymerases. Purine core compounds, especially the 2,6,9-substituted purines, act as potent inhibitors of Hsp90, Src kinase, P38 alpha MAP kinase, sulfotransferases, phosphodiesterases, and Cdks. Accordingly, the developement of more efficient, convenient, and environmentally friendly methods for the synthesis of 2,6,9-substituted purines is important. 2,6,9-Substituted purines were synthesized previously by Fiorini et al. using solution-phase synthetic approaches with 2,6-dichloropurine as the starting material. However, this synthetic process needs a long heating time and complicated reaction conditions. Subsequently, several solid-phase synthesis methods were developed, but the substitution at the C2 position was difficult. To expand the diversity of the N9 position of purine, Ding et al. employed a copper(II)-mediated coupling reaction to prepare 9-arylpurines with yields of 43- 47%. The coupling reaction has emerged as a valuable method for the preparation of 9-arylpurines, but long reaction times are required.