Synthesis of fluorinated purine and 1-deazapurine glycosides as potential inhibitors of adenosine deaminase

Abstract

The synthesis of 2- and 6-trifluoromethylated purines and 1-deazapurines was performed by formal [3 + 3]-cyclization reactions of 5-aminoimidazoles with a set of trifluoromethyl-substituted 1,3-CCC- and 1,3-CNC-dielectrophiles. The corresponding fluorinated nucleosides were synthesized by glycosylation of 9-unsubstituted purines and 1-deazapurines with peracetylated β-ribose, β-glucose, and rhamnose and subsequent deprotection. These scaffolds can be considered as potential inhibitors of adenosine deaminase (ADA) and inosine monophosphate dehydrogenase (IMPDH) enzymes.