Exploring an Optimised Approach for Converting 6-Thioguanosine Derivatives to Asymmetric Disulphides

Here we present a systematic analysis of the synthesis of unsymmetrical disulphides employing 6-thioguanosine and its mono- and dinucleotides by three of the most common strategies: a nucleophilic substitution of the thiol, a thiol exchange reaction with another disulphide and oxidative dehydrogenation coupling reactions of S-H bonds. The exchange reaction was found to be the most efficient approach and could be used not only for nucleosides but also for nucleotides. Here we present the systematic analysis of conversion of 6-thioguanosine derivatives into unsymmetrical disulphides. Within the work we explored three known strategies for the preparation of disulphide bonds for 6-thioguanosine and its phosphorylated derivatives. We have shown that obtained derivatives are stable under certain conditions and can be easily further expanded using various tags depending on need.+ image