2-(Phenylthio)ethyl as a Novel Two-Stage Base Protecting Group for Thymidine Analogues

2-(Phenylthio)ethyl is here proposed for temporary masking the thymine residue in the synthesis of sugar modified thymidine derivatives. This protection has been devised as a ʹtwo-stageʹ system. The 2-(phenylthio)ethyl residue can be easily and regiospecifically inserted at the N3-position of the pyrimidine by a Mitsunobu reaction with 2-(phenylthio)ethanol and is perfectly stable also to strongly basic conditions. This allowed us to selectively achieve O-alkylation of the ribose moieties in satisfactory yields, avoiding undesired base alkylations. After oxidation of the thioether to sulfone, the thymine protecting group can be totally removed, by a (beta)elimination mechanism, upon the same basic treatment required for the final deprotection and detachment of oligonucleotides from the support in solid-phase synthesis protocols.