Synthetic Studies on Phosphorylating Reagent. IV. A Novel Synthesis of Nucleoside-3′,5′ Cyclic Phosphates by the Use of 2-(N,N-Dimethylamino)-4-nitrophenyl Phosphate

A novel method for the synthesis of nucleoside-3′,5′ cyclic phosphate has been investigated. The intermediates, nucleoside-5′ 2-(N,N-dimethylamino)-4-nitrophenyl phosphates (3a–d), were prepared in good yields by the condensation of unprotected nucleosides with 2-(N,N-dimethylamino)-4-nitrophenyl phosphate (2), using dicyclohexylcarbodiimide (DCC) in dimethylformamide (DMF). Treatment of the intermediates 3a–d with acetic acid in boiling pyridine under high dilution condition gave nucleoside-3′,5′ cyclic phosphates in fairly good yields and small amount of other nucleotides, whereas nucleoside-2′,3′ cyclic phosphate was obtained by the reaction in DMF at 100 °C. An attempt at the direct synthesis of the cyclic nucleotide by refluxing the reaction mixture of unprotected nucleoside with DCC and 2 in pyridine was also successful to afford the similar results as in the stepwise procedure.