Therapeutic Oligonucleotides, ch 2: Diverse Dinucleotides Containing 3′-S-Phosphorothiolate Linkages

Abstract

Abstract The 3′-S-phosphorothiolate (3′-SP) linkage has proven to be a very useful analogue of the phosphodi- ester 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 cor- responding 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 phos- phites and also simplifies the deprotection strategy. Full experimental details and spectroscopic data for the synthetic intermediates and the target dinucleotide are provided. Key