Dithymidine phosphorothioate

The 4-chloro-2-nitrobenzyl group was useful in the synthesis of dithymidine phosphorothioates. It could be cleaved with a minimun of side reactions with PhSH, TEA. Pyr. ... 

Example 3 different activators derived from 4,5-dicyanoimidazole were prepared and used by Just and Lu in the stereoselective coupling reactions of phosphoroamidites with nucleosides [19]. An easily removable chiral auxiliary derived from d-xylose was synthesized and used for stereoselective construction of dithymidine phosphorothioate. The part of this study is illustrated below. 

The first synthesis of a dinucleotide analogue combining phosphorothioate and boranophosphate features has been reported. To prepare dithymidine boranophosphorothioate (71), Fmoc-protected thymidine was phosphitylated by bis(diisopropylamino)-chlorophosphine in the presence of DMAP. The resulting phosphoramidite was treated in situ with a 3 -protected thymidine and tetrazole and was then converted to a phosphite triester with nitrophenol. The phosphite triester was subsequently treated with BH3-SMe2 followed by LiS2 in the presence of 18-crown-6 to yield (71). This novel type of dinucleoside... 

The dithymidine phosphorothiofluoridates 67 have been prepared as a mixture of diastereoisomers following treatment of the methylselenyl ester precursors 68 with tetrabutylammonium fluoride. The base-catalysed hydrolysis of the phosphorothiofluoridates was found to be about four times slower than the corresponding phosphorofluoridates. The conversion of dinucleoside phosphorothioates 69 and dinucleoside phosphorodithioates 70 into the corresponding phosphorofluoridates 71 and phosphorothiofluoridates 72 respectively using iodine and triethylamine trishydrofluoride in acetonitrile has also been described. The conversions are rapid and occurred in excellent yield. 

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