Solid phase synthesis and purification of 5'-mercaptoalkylated oligonucleotides

A novel strategy for the synthesis of thiol link phosphoramidites having base labile S-acyl type protecting groups is described. The method involves the reaction of 6-bromohexanol with potassium thioacetate or thiobenzoate in the presence of 18-crown-6 as a phase transfer catalyst to obtain the compounds 3(a,b) which were then converted to their corresponding phosphoramidites 4(a,b) and used for solid phase synthesis of 5'-mercaptoalkylated oligonucleotides. The thiolated oligomers were purified by single step covalent chromatography using an activated sulfhydryl group containing support.