合成路线1

In an alternative, solid-phase method, O-protection of decitabine (I) by means of HMDS in DMF, followed by N-acylation of the obtained bis-TMS ether (X) with phenoxyacetic anhydride (XI) in pyridine gives amide (XII). Desilylation of compound (XII) using TASF in DMF, followed by selective protection of the primary alcohol group in the resulting diol (XIII) with 4,4’-dimethoxytrityl chloride (DMT-Cl) in pyridine furnishes ether (XIV). Condensation of the free secondary alcohol of (XIV) with 2-cyanoethyl N,N,N’,N’-tetraisopropylphosphorodiamidate (V) using benzylthiotetrazole (BTT) in acetonitrile provides phosphoramidate (XV), which is then condensed with the 3’-deoxyguanosine derivative (XVI) linked onto controlled pore glass (CPG) support in the presence of BTT in MeoH to afford trisubstituted phosphite (XVII) . oxidation of phosphite (XVII) with t-BuOOH in acetonitrile provides the corresponding phosphate (XVIII), which is then O-deprotected by means of Cl2CHCOOH in toluene to give the primary alcohol (XIX). Finally, CPG-bound dinucleotide (XIX) is submitted to deprotection and cleavage from the solid support with aqueous Et3N·AcOH, followed by precipitation of the resulting triethylammonium salt in the presence of naClo4 in H2O/acetone .