Dinucleotides Containing 3-S-Phosphorothiolate Linkages

The 3′-S -phosphorothiolate (3′-SP) linkage has proven to be a very useful analogue of the phosphodiester group in nucleic acid derivatives; it is achiral and also shows good resistance to nucleases. Whilst oligonucleotides containing a 3′-SP linkage are best prepared using phosphoramidite chemistry, the corresponding dinucleotides are most efficiently synthesised using a Michaelis–Arbuzov reaction between a nucleoside 5′-phosphite and a nucleoside 3′-S -disulphide. The method described here is for a thymidine dinucleotide and is based on the use of a silyl phosphite, which is more reactive than simple alkyl phosphites and also simplifies the deprotection strategy. Full experimental details and spectroscopic data for the synthetic intermediates and the target dinucleotide are provided.