Synthesis of nucleoside phosphoroselenolates via the efficient Michaelis–Arbuzov reaction of selenocyanates

Modified internucleoside linkages for nuclease-resistant oligonucleotides

“…This modification has not been further studied for years with the exception of the use of 3′-SeP-ODN by Kool and co-workers for templated-directed chemical ligation 149 and a new method developed by Vyle for the synthesis of nucleoside selenophosphates via the efficient Michaelis–Arbuzov reaction of selenocyanates. 150 The authors were able to synthetize a selenophosphate dimer with high efficiency.…”

Sweet Selenium: Synthesis and Properties of Selenium-Containing Sugars and Derivatives

“…The presence of 2,6-lutidine served to improve the solubility of 100 in CH 3 CN, and all the dimers were obtained as diasteroisomers. Finally, the phosphitylation of the dimers allowed the preparation of the corresponding phosphoramidites 103 , which were then used as starting materials for the successive solid-state synthesis of oligomers, the actual target of these studies [ 93 , 94 ]. These selenium containing oligomers were used to observe conformational changes within nucleic acids during folding, recognition, and processing by applying the selenium single wavelength anomalous diffraction.…”

Solid-phase synthesis and structural characterisation of phosphoroselenolate-modified DNA: a backbone analogue which does not impose conformational bias and facilitates SAD X-ray crystallography

“…However, a single major peak with signicantly longer retention time (t R ¼ 38.7 min) was identied as the dimer TpSedT following coinjection with an authentic sample. 49 Previously, Stec and coworkers examined nuclease digestion of putative TpSedT and described using ten times the quantity of enzyme required to effect cleavage of the corresponding phosphorothioate substrate. During this treatment, formation of the corresponding diselenide; (SedT) 2 , was observed and this compound is assumed to be the origin of a novel hydrophobic material (t R ¼ 45.1 min) which was also apparent during extended treatment of pure TpSedT with snake venom.…”

“…These are achiral and potentially more stable than the corresponding phosphoroselenoates but have been documented in only a very limited number of communications. [47][48][49] Alkylation of the lead salt of O,O-diethylphosphoroselenoate was rst reported in 1911 50 and this strategy has been applied to the preparation of internucleotide phosphoroselenolate linkages using 5 0 -halothymidine derivatives either in DMF 47 or under aqueous conditions. 48 In the former case, characterisation of the dimer product was equivocal indicating that perhaps both O-and Se-alkylation had occurred.…”

“…In contrast, Michaelis-Arbuzov (M-A) reaction of a nucleoside 3 0 -H-phosphonate with a 5 0 -selenocyanate enabled synthesis of a fully-characterised phosphoroselenolate-bridged dimer (TpSedT) with high efficiency. 49 Herein, we describe the further developments to this methodology enabling the isolation of pure dinucleoside phosphoroselenolate triesters in good to excellent yields, their subsequent phosphitylation and efficient introduction into oligodeoxynucleotides under solid-phase conditions. Furthermore, we report a model DNA crystal structure incorporating this modication which evinces an A-form morphology with minimal perturbation of the backbone.…”