Synthesis and properties of N-tritylthio nucleoside derivatives and reductive removal of the tritylthio group by use of tributyltin hydride and tris(trimethylsilyl)silane

Abstract

N-Sulfenylations of ribo- and deoxyribo- nucleoside derivatives have been studied by the use of triphenylmethanesulfenyl chloride as a sulfenylating reagent under a variety of conditions. A two-phase system using 0.2 mol dm^–3 Na₂CO₃–CH₂Cl₂ was found to be effective for N-sulfenylation of deoxycytidine, deoxyadenosine and guanosine derivatives (7b, 9b, 9c and 11d), which were partially or fully protected at the hydroxy functions. In the case of adenosine 9c, the N¹-sulfenylated deoxyadenosine derivative 10f was also formed. For the N-sulfenylation of the 5′-protected thymidine derivative 7a, phase-transfer catalysis was successfully used. It was found that the N-TrS group could be removed by reductive C–S bond cleavage using Bu₃SnH or (Me₃Si)₃SiH in toluene in the presence of AIBN under reflux for 5 min. In several cases, the Bu₃SnH-mediated deprotection occurred in the absence of AIBN. When triethylborane or sonication was used as a radical initiator, the cleavage reaction could be carried out at room temperature. The stability of the TrS group attached to these nucleoside bases was examined under several acidic and basic conditions.