A Valuable Synthetic Intermediate for 2-Substituted Adenosine

Adenosine derivatives play important roles in metabolic actions in various cells, and show antiviral and anticancer activities. 2-Iodoadenosine (1) is a valuable synthetic intermediate for the preparation of 2-substituted adenosine derivatives. Here are two typical adenosine derivatives syntheses using cross-coupling reactions. Matsuda et al. have reported a synthesis of 2-alkynyladenosines using a palladium-catalyzed cross-coupling reaction, and evaluation of their pharmacological activities.¹⁾ Zhao and Baranger have reported a synthesis of 2-alkenyladenosines using the Heck reaction.²⁾

Typical Procedure^1c):
2-Iodoadenosine (393 mg), CuI (9.5 mg), bis(triphenylphosphine)palladium(II) dichloride (36 mg), triethylamine (0.16 mL) and ethynylbenzene (123 mg) in DMF (7 mL) are heated at 80 °C for 1 h. After 2-iodoadenosine is completely consumed, the reaction mixture is concentrated to dryness under reduced pressure. The residue is dissolved in CHCl₃, and H₂S gas is introduced to the solution (~30 s) followed by N₂ gas. The suspension is filtered through a Celite pad and washed with CHCl₃. The combined filtrate is concentrated to dryness in vacuo, and the residue is purified by silica gel column chromatography (eluent: MeOH–CHCl₃) to give 2-(phenylethyn-1-yl)adenosine (373 mg, Y. 97%).