Application of germyldesulfonylation reactions to the synthesis of germanium-containing nucleoside analogues

摘要

Treatment of the protected (E)-5′-deoxy-5′-[(p-toluenesulfonyl)methylene]uridine and adenosine derivatives with tributyl- or triphenylgermane hydride (AIBN/toluene/Δ) effected radical-mediated germyldesulfonylations to give 5′-(tributyl- or triphenylgermyl)methylene-5′-deoxyuridine and adenosine derivatives as single (E)-isomers. Analogous treatment of 2′-deoxy-2′-[(phenylsulfonyl)methylene]uridine with Ph3GeH afforded the corresponding vinyl triphenylgermane product. Stereoselective halodegermylation of the (E)-5′-(tributylgermyl)methylene-5′-deoxy nucleosides with N-iodosuccinimide or N-bromosuccinimide provided the Wittig-type (E)-5′-deoxy-5′-(halomethylene) nucleosides quantitatively, while no halodegermylations was observed with the 5′-deoxy-5′-(triphenylgermyl)methylene counterparts. Treatment of the vinyl trialkylgermanes with aqueous trifluoroacetic acid effected protiodegermylation, while vinyl triarylgermanes were stable under the acidic conditions.