Glycosyl phosphorothioates

Scheme 46. Glycosyl phosphorodithioates (171), glycosyl phosphorothioates (172) and glycosyl phosphoroselenoates (173).

Bielawska and Michalska [511] have introduced S-(2-deoxyglycosyl)phosphor-othioates as glycosyl donors. Activation of these compounds for glycosidation with silver salts (AgF, AgC104 or AgOTf) resulted in the formation of 2 -deoxydisacchar-ides as anomeric mixtures. Thiem and coworkers reported [507] an efficient activation method for S-(2-deoxyglycosyl)phosphorothioate donors 102 by using N-iodo-succinimide (NIS) or iodonium bis(2,4,6-trimethylpyridine) perchlorate (IDCP) (Scheme 4.94). 

This improvement allowed achieving the synthesis of 2-deoxy disaccharide 103 with high stereoselectivity and good yield in short reaction times. The composition of the reaction mixture was found to be practically independent of the configuration of the S-(2-deoxy-D-glucopyranosyl)phosphorothioate. These results seem to provide an evidence that this glycosylation procedure proceeds via the SN1 displacement reaction mechanism. 

Isosteric analogues of glycosyl phosphates phosphorothioates, boranophosphates, phosphoroamidates... 

Nucleoside 5 -phosphorothioates have also been employed as activated nucleotide derivatives for synthesis of pyrophosphates.321 The interaction of tributylammonium 2, 3 -di-0-benzoyluridine 5 -phosphorothioate (73) with silver a-D-glucopyranosyl and a-D-galac-topyranosyl phosphates in pyridine solution, with subsequent de-benzoylation, gave the corresponding glycosyl esters in 60-70% yield. This procedure can probably be classified as a variant of the mixed-anhydride method, the driving force of the reaction being the formation of insoluble silver sulfide. 

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