Two-Step, One-Pot Synthesis of Inosine, UNIT 1.26 Guanosine, and 2!-Deoxyguanosine O6-Ethers via Intermediate O6-(Benzotriazol-1-yl) Derivatives

Abstract

A simple method for the etherification at the O6-position of silyl-protected inosine, guanosine, and 2'-deoxyguanosine is described. Typically, a THF solution of the silylated nucleoside is treated with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and Cs2CO3 under a nitrogen atmosphere. Conversion to the O6-(benzotriazol-1-yl) ethers occurs within about 10 min for inosine, and within about 60 min for guanosine and 2'-deoxyguanosine. Then, for reaction with alcohols, the reaction mixture is evaporated and the O6-(benzotriazol-1-yl) ether is treated with Cs2CO3 and an appropriate alcohol, at room temperature. On the other hand, for reaction with phenols, Cs2CO3 and the appropriate phenol are added to the reaction mixture without evaporation, and the reaction is carried out at 70"C. Subsequently, workup, isolation, and purification lead to the requisite O6-alkyl or O6-aryl ethers in good to excellent yields.