Two-step, one-pot synthesis of inosine, guanosine, and 2'-deoxyguanosine O6-ethers via intermediate O6-(benzotriazol-1-yl) derivatives.
A simple method for the etherification at the O(6)-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 Cs(2)CO(3) under a nitrogen atmosphere. Conversion to the O(6)-(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 O(6)-(benzotriazol-1-yl) ether is treated with Cs(2)CO(3) and an appropriate alcohol, at room temperature. On the other hand, for reaction with phenols, Cs(2)CO(3) 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 O(6)-alkyl or O(6)-aryl ethers in good to excellent yields.
The City College and The City University of New York, New York City, NY, USA.
Hari Prasad
HP
Kokatla
Mahesh K
MK
Lakshman
D002254:Carbonates / Q000737:chemistry; D002586:Cesium / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004987:Ethers / Q000138:chemical synthesis; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007288:Inosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry*
D002254:Carbonates; D004987:Ethers; D009943:Organophosphorus Compounds; D014230:Triazoles; D006151:Guanosine; D002586:Cesium; D007288:Inosine; D003849:Deoxyguanosine; C545311:cesium carbonate