32909-05-0Relevant articles and documents
Electron-deficient benzotriazoles for the selective N-acetylation of nucleosides
Reid, Andrew K.,McHugh, Callum J.,Richie, Graham,Graham, Duncan
, p. 4201 - 4203 (2006)
The use of an acetylated benzotriazole for the selective protection of the amino groups of cytidine and 2′-deoxycytidine is reported. The use of the acetyl group is of considerable interest industrially in this role, and a single-step protection strategy advantageous in bulk production. 1-Acetyl-4-nitrobenzotriazole was found to readily acetylate the amine of cytidine preferentially over the exposed alcohol functionalities. With adaptation of the protocol, 2′-deoxycytidine was protected using the same reagent. A similar approach was attempted for the benzoylation of adenosine but was found to be unsuitable.
Chlorothioketene, the ultimate reactive intermediate formed by cysteine,conjugate β-lyase-mediated cleavage of the trichloroethene metabolite S-(1,2-dichlorovinyl)-L-cysteine, forms cytosine adducts in organic solvents, but not in aqueous solution
Voelkel, Wolfgang,Dekant, Wolfgang
, p. 1082 - 1088 (2007/10/03)
Chlorothioketene has been suggested as a reactive intermediate formed by the cysteine conjugate β-lyase-mediated cleavage of S-(1,2-dichlorovinyl)- L-cysteine, a minor metabolite of trichloroethene. Halothioketenes are highly reactive, and their intermediate formation may be confirmed by reactions such as cycloadditions and thioacylations of nucleophiles. A precursor of chlorothioketene, S-(1,2-dichlorovinyl)thioacetate, is readily accessible by the reaction of dichloroethyne with thioacetic acid. In presence of base, S- (1,2-dichlorovinyl)thioacetate is cleaved to chlorothioketene. Chlorothioketene is not stable at room temperature and was characterized after transformation to stable products by reaction with compounds such as cyclopentadiene, N,N-diethylamine, and ethanol. In organic solvents, the cleavage of S-(1,2-dichlorovinyl)thioacetate in the presence of cytosine results in N4-acetylcytosine, N4-(chlorothioacetyl)cytosine; and small amounts of 3-(N4-thioacetyl)cytosine. No reaction products were seen with guanosine, adenosine, and thymidine under identical conditions. When cytosine was reacted with S-(1,2-dichlorovinyl)thioacetate in aqueous solutions, only N4-acetylcytosine was formed. N4-(Chlorothioacetyl)cytosine and 3-(N4- thioacetyl)cytosine were not detected even when using a very sensitive method, derivatization with pentafluorobenzyl bromide and electron capture mass spectrometry with a detection limit of 50 fmol/μL of injection volume. Aqueous solutions of DNA cleave S-(1,2-dichlorovinyl)thioacetate to give N4- acetyldeoxycytidine in DNA, but chlorothioketene adducts of deoxynucleosides were also not detected in these experiments. These results confirm the electrophilic reactivity of chlorothioketene toward nucleophilic groups of DNA constituents in inert solvents but also demonstrate that the formation of DNA adducts under physiological conditions likely is not efficient. Therefore, DNA adducts may not represent useful biomarkers of exposure and biochemical effects for trichloroethene.
Processes for synthesizing nucleotides and modified nucleotides using N
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, (2008/06/13)
Disclosed herein are protecting groups for exocyclic amino groups of the base cytosine for use in the synthesis of oligonucleotides and oligonucleoside phosphorothioates, the protecting groups being represented by the formula: --CO--(CH2)0-9 --CH3. In a particularly preferred embodiment, the base cytosine is protected with acetyl (--CO--CH3), and the oligonucleotide or oligonucleoside phosphorothioate incorporating the protected cytosine is subjected to a cleavage/deprotection reagent comprising methylamine and ammonia.