Improved synthesis of oligonucleotides containing 2-thiouridine derivatives by use of diluted iodine solution

It is known that the 2-thiocarbonyl group of 2-thiouridine (s2U) derivatives reacts easily with various oxidizing agents used in oligonucleotide synthesis to give a complex mixture. In this letter, we report an improved method for the synthesis of oligonucleotides containing s2U derivatives. It turned out that the 2-thiocarbonyl group of oligonucleotides containing s2U derivatives was stable in a 0.02 M solution of iodine in pyridine–THF–H2O. These conditions were successfully applied to the synthesis of oligonucleotides containing s2U derivatives on an automated DNA/RNA synthesizer. Moreover, no undesirable side reactions were detected so that these modified oligonucleotides could be obtained in markedly improved yields.