Two‐Step, One‐Pot Synthesis of Inosine, Guanosine, and 2′‐Deoxyguanosine O6‐Ethers via Intermediate O6‐(Benzotriazol‐1‐yl) Derivatives
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Abstract
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 Cs2 CO3 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 Cs2 CO3 and an appropriate alcohol, at room temperature. On the other hand, for reaction with phenols, Cs2 CO3 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. Curr. Protoc. Nucleic Acid Chem. 49:1.26.1?1.26.16. © 2012 by John Wiley & Sons, Inc.
Keywords: inosine; guanosine; 2??deoxyguanosine; BOP; reactive nucleosides; ethers; benzotriazolyl
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Figure 1.26.1 Substrates and alcohols used for the two‐step, one‐pot etherification, product numbers, and corresponding yields. View Image -
Figure 1.26.2 Plausible mechanism for the activation of the C‐6 amide in inosine nucleosides and conversion to adenosine derivatives. View Image -
Figure 1.26.3 Two possible modes by which the C‐6 amide could react with BOP leading to O 6 ‐(benzotriazol‐1‐yl)inosine derivatives. View Image -
Figure 1.26.4 Synthesis of silylated nucleoside precursors, their conversion to the O 6 ‐(benzotriazol‐1‐yl) derivatives (which are not isolated), and conversion to the O 6 ‐alkyl and O 6 ‐aryl ethers. View Image
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Literature Cited
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