173170-12-2Relevant articles and documents
Preparation of 2′-Alkylselenouridine Derivatives via a 2-(Trimethylsilyl)ethylselenation Approach
Fukuno, Shota,Ninomiya, Masayuki,Koketsu, Mamoru
, p. 831 - 834 (2017)
2′-O-Methylation of nucleotides is well-known to increase siRNA stability against nuclease activities. Recently, selenium-containing biomolecules have been recognized as unique biological and medicinal agents for humans. In this study, 2′-alkylselenouridine derivatives were prepared through 2-(trimethylsilyl)ethylselenation at the C2′ position of 5′-DMT-2,2′-O-cyclouridine, followed by alkylation with various haloalkanes utilizing the characteristics of a Si atom. Overall, we demonstrated the versatility of a 2-(trimethylsilyl)ethylselenyl group for the synthesis of 2′-alkylselenouridines.
Regioselective Mitsunobu Reaction of Partially Protected Uridine
Szlenkier, Maurycy,Kamel, Karol,Boryski, Jerzy
, p. 410 - 425 (2016/08/05)
Mitsunobu reaction of partially acylated uridine proceeds with high regioselectivity for intramolecular SN2 anhydro linkage closuring. Under the reaction conditions, an isomeric mixture of diacyl uridine derivatives with either free 2′- or 3′-hydroxyl group was transformed into a single cyclonucleosidic product, 2,2′-anhydro-3′,5′-di-O-acyluridine. This paper presents a possible mechanism of the reactions, the explanation of observed phenomenon based on semiempirical and density functional theory (DFT) calculations and possible utility of this synthetic pathway.
Synthesis of spin-labeled riboswitch RNAs using convertible nucleosides and DNA-catalyzed RNA ligation
Büttner, Lea,Seikowski, Jan,Wawrzyniak, Katarzyna,Ochmann, Anne,H?bartner, Claudia
, p. 6171 - 6180 (2013/10/21)
Chemically stable nitroxide radicals that can be monitored by electron paramagnetic resonance (EPR) spectroscopy can provide information on structural and dynamic properties of functional RNA such as riboswitches. The convertible nucleoside approach is used to install 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and 2,2,5,5-tetramethylpyrrolidin-1-oxyl (proxyl) labels at the exocyclic N4-amino group of cytidine and 2′-O-methylcytidine nucleotides in RNA. To obtain site-specifically labeled long riboswitch RNAs beyond the limit of solid-phase synthesis, we report the ligation of spin-labeled RNA using an in vitro selected deoxyribozyme as catalyst, and demonstrate the synthesis of TEMPO-labeled 53 nt SAM-III and 118 nt SAM-I riboswitch domains (SAM = S-adenosylmethionine).
New telluride-mediated elimination for novel synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides
Sheng, Jia,Hassan, Abdalla E. A.,Huang, Zhen
, p. 3725 - 3729 (2008/09/20)
(Chemical Equation Presented) Several 2′,3′-dideoxynucleosides (ddNs) and 2′,3′-didehydro-2′,3′-dideoxynucleosides (d4Ns) are FDA-approved anti-HIV drugs. Via conveniently synthesized 2,2′-anhydronucleosides, we have developed a novel synthesis of d4Ns by discovering and applying a new telluride-mediated elimination reaction. Our experiment results show that after substitution of 2,2′-anhydronucleosides with a telluride monoanion, a telluride intermediate is formed, and its elimination leads to formation of the olefin products (d4Ns). Our mechanistic study indicates that this telluride-assisted reaction consists of two steps: substitution (or addition) and elimination. By using dimethyl ditelluride (0.1 equiv) as the reagent, d4Ns can be synthesized with yields up to 90% via this telluride-mediated elimination. Our novel strategy has great potential to simplify synthesis of these drugs and to further reduce cost of AIDS treatment and will also facilitate development of novel d4N and ddN analogues.
Chemical Synthesis of Selenium-Modified Oligoribonucleotides and Their Enzymatic Ligation Leading to an U6 SnRNA Stem-Loop Segment
Hoebartner, Claudia,Micura, Ronald
, p. 1141 - 1149 (2007/10/03)
The derivatization of nucleic acids with selenium is highly promising to facilitate nucleic acids structure determination by X-ray crystallography using the multiwavelength anomalous dispersion (MAD) technique. The foundation for such an approach has been laid by Huang, Egli, and co-workers and was exemplified on small DNA duplexes. Here, we present a comprehensive study on the preparation of RNAs containing 2′-Se-methylpyrimidine nucleoside labels. This includes the synthesis of a novel 2′-Semethylcytidine phosphoramidite 11 and its incorporation into oligoribonucleotides by solid-phase synthesis. Deprotection of the oligonucleotides is achieved in the presence of millimolar amounts of threo-1,4-dimercapto-2,3-butandiol (DTT). With this additive, oxidation products and follow-up side-products are suppressed and acceptable HPLC traces of the crude material are obtained, so far tested for sequences of up to 22-mers. Moreover, an extensive investigation on the enzymatic ligation of the selenium-containing oligoribonucleotides demonstrates the high flexibility of the selenium approach. Our target sequence, an U6 snRNA stem-loop motif comprising all naturally occurring nucleoside modifications beside the Selabel is achieved by ligation using T4 RNA ligase.
Efficient synthesis of 2′,3′-dideoxy-2′-amino-3′- thiouridine
Dai, Qing,Piccirilli, Joseph A.
, p. 2169 - 2172 (2007/10/03)
Metal ion rescue experiments provide a powerful approach to establish the presence and role of divalent metal ions in the biological function of RNA. The utility of this approach depends on the availability of suitable nucleoside analogues. To expand the
Internal derivatization of oligonucleotides with selenium for x-ray crystallography using MAD
Du,Carrasco,Teplova,Wilds,Egli,Huang
, p. 24 - 25 (2007/10/03)
We have developed a route for the synthesis of 2′-selenium uridine analogues and oligonucleotides containing selenium labels, and have demonstrated for the first time a new strategy to covalently derivatize nucleotides with selenium for phase and structur
Synthesis of oligodeoxyribonucleotide bearing 2'-S-alkyl residue and its effect on the duplex stability
Ozaki, Hiroaki,Sato, Yuichi,Azuma, Sadaji,Sawai, Hiroaki
, p. 593 - 601 (2007/10/03)
2'-Deoxy-2'-S-hexyluridine derivative was synthesized from 2,2'- anhydrouridine and 1-hexanethiol and incorporated into an oligodeoxyribonucleotide. The thermal stability of the duplexes formed by the 2'-S-hexyl modified ODN with either the complementary DNA or RNA strand was decreased compared to the unmodified counterparts.
Nucleosides and nucleotides. 180. Synthesis and antitumor activity of nucleosides that have a hydroxylamino group instead of a hydroxyl group at the 2'- or 3'-position of the sugar moiety
Ogawa, Akira,Tanaka, Motohiro,Sasaki, Takuma,Matsuda, Akira
, p. 5094 - 5107 (2007/10/03)
The design and synthesis of potential antitumor antimetabolites 2'- deoxy-2'-(hydroxylamino)uridine (15), -cytidine (19, 2'-DHAC), and -adenosine (35), their regioisomers, 3'-deoxy-3'-(hydroxylamino)uridine (40) and - cytidine (45, 3'-DHAC), and their 2'-deoxy analogues, 2',3'-dideoxy-3'- (hydroxylamino)uridine (49) and -cytidine (52, 3'-dDHAC), are described. We measured the pK(a) values of the hydroxylamino group in 15 and 40 using 13C NMR spectroscopy as a function of pH to be 2.9 and 3.4, respectively. We also found that these nucleosides gradually decomposed in neutral solution but not in acidic solution. This decomposition may be related to the generation of aminoxy radicals at the sugar moiety. The in vitro cytotoxicity of these nucleosides was evaluated using L1210 and KB cells. 2'-DHAC (19) inhibited the growth of L1210 and KB cells, with IC50 values of 1.58 and 1.99 μM, respectively. 3'-DHAC (45) and 3'-dDHAC (52) were also cytotoxic against L1210 cells, with IC50 values of 4.03 and 1.84 μM, respectively, but not against KB cells. The cytotoxicity of 2'-DHAC (19) and 3'-DHAC (45) against L1210 cells in vitro was reversed by the addition of cytidine, while that of 3'-dDHAC (52) was reversed by 2'-deoxycytidine. 2'-DHAC (19) and 3'-dDHAC (52) mainly inhibited DNA synthesis in L1210 cells, while 3'-DHAC (45) inhibited RNA synthesis. We also evaluated the antitumor activities of 2'- DHAC (19) and 3'-DHAC (45) against murine Meth-A fibrosarcoma cells in vivo. 2'-DHAC (19) was more active than 3'-DHAC (45) when administered intravenously on days 1-10 consecutively at 10 mg/kg/day. 2'-DHAC (19) inhibited tumor growth at a rate of 66.9%.
Novel intramolecular introduction of nucleophiles to 2,2′-anhydrouridine
McGee, Danny P. C.,Vaughn-Settle, Alecia
, p. 1095 - 1097 (2007/10/03)
2′-N-alkyluridine nucleosides are synthesized via intramolecular reaction of alkyl isocyanates with 5′-O-protected-2,2′-anhydrouridine. Copyright
