- Efficient assessment of modified nucleoside stability under conditions of automated oligonucleotide synthesis: Characterization of the oxidation and oxidative desulfurization of 2-thiouridine
-
In order to efficiently assess the chemical stability of modified nucleosides to the reagents and conditions of automated oligonucleotide synthesis, we designed, developed and tested a scheme in which the modified nucleoside, directly attached to a solid support, is exposed to the cyclic chemistry of the instrument. Stability of 2-thiouridine against different oxidizers was investigated. Tertbutyl hydroperoxide (1 M) in anhydrous acetonitrile was a more effective oxidizer for the incorporation of 2-thiouridine into oligonucleotide chains than the same oxidizer in methylene chloride. Carbon tetrachloride/water in the presence of a basic catalyst was superior in maintaining the thiocarbonyl function, but its utility for RNA synthesis has yet to be fully tested, whereas 2-phenylsulfonyloxaziridine was a very efficient reagent for oxidative desulfurization of 2-thiouridine.
- Sochacka
-
-
Read Online
- A prebiotically plausible synthesis of pyrimidine β-ribonucleosides and their phosphate derivatives involving photoanomerization
-
Previous research has identified ribose aminooxazoline as a potential intermediate in the prebiotic synthesis of the pyrimidine nucleotides with remarkable properties. It crystallizes spontaneously from reaction mixtures, with an enhanced enantiomeric excess if initially enantioenriched, which suggests that reservoirs of this compound might have accumulated on the early Earth in an optically pure form. Ribose aminooxazoline can be converted efficiently into α-ribocytidine by way of 2,2'-anhydroribocytidine, although anomerization to β-ribocytidine by ultraviolet irradiation is extremely inefficient. Our previous work demonstrated the synthesis of pyrimidine β-ribonucleotides, but at the cost of ignoring ribose aminooxazoline, using arabinose aminooxazoline instead. Here we describe a long-sought route through ribose aminooxazoline to the pyrimidine β-ribonucleosides and their phosphate derivatives that involves an extraordinarily efficient photoanomerization of α-2-thioribocytidine. In addition to the canonical nucleosides, our synthesis accesses β-2-thioribouridine, a modified nucleoside found in transfer RNA that enables both faster and more-accurate nucleic acid template-copying chemistry.
- Xu, Jianfeng,Tsanakopoulou, Maria,Magnani, Christopher J.,Szabla, Rafa?,?poner, Judit E.,?poner, Ji?í,Góra, Robert W.,Sutherland, John D.
-
p. 303 - 309
(2017/04/03)
-
- Reactions of Alkoxyuridines with Ammonia (l)
-
2-Alkoxy- and 4-alkoxyuridines were converted into isocytidine and cytidine by reaction with ammonia at room temperature.Reaction with hydrogen sulfide produced 2-thio- and 4-thiouridine but the reaction was incomplete.The reaction may be helpful in the identification of alkylated pyrimidine nucleosides in DNA.
- Mathews, Robert A.,Stoehrer, Gerhard
-
p. 1601 - 1602
(2007/10/02)
-
