Synthesis and properties of dithymidine phosphate analogues containing 3'-thiothymidine.
Dithymidine-3'-S-phosphorothioate (d(TspT)) has been prepared from a 5'-O-monomethoxytritylthymidine-3'-S-phosphorothioamidite (7) by activation with 5-(p-nitrophenyl)tetrazole in the presence of 3'-O-acetylthymidine. The resulting dinucleoside phosphorothioite is readily oxidised to the corresponding 3'-S-phosphorothioate using either tetrabutylammonium (TBA) periodate or TBA oxone and has been deprotected under standard conditions to yield d(TspT). This dithymidine phosphate analogue is comparatively resistant to hydrolysis by nuclease P1, but the P-S bond is readily cleaved by aqueous solutions of either iodine or silver nitrate. Dithymidine-3'-S-phosphorodithioate (d[Tsp(s)T]) was prepared in an analogous fashion using sulphur to oxidise the intermediate dinucleoside phosphorothioite. Absolute stereochemistry has been assigned to the diastereoisomers of d[Tsp(s)T] by comparing their physical and chemical properties to those of the dinucleoside phosphorothioates.
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Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, UK.
Vyle
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D015226:Dinucleoside Phosphates / Q000138:chemical synthesis*; D006868:Hydrolysis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009946:Organothiophosphorus Compounds; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives*
D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; D009946:Organothiophosphorus Compounds; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013936:Thymidine