Regioselective 1‐Alkylation of 2′‐Deoxyguanosine.

Huang, Yanhe; Johnson, Francis

doi:10.1002/chin.200310202

Cited by 5 publications

(7 citation statements)

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“…Starting from commercially available 5′- O -dimethoxytrityl-2′-deoxyinosine, the free 3′-alcohol was protected as a tert -butyldimethylsilyl ether to produce 1 in 94% yield. Then, regioselective alkylation at the N 1 position was accomplished with 1-bromo-2-chloroethane in the presence of Cs 2 CO 3 to produce the chlorinated adduct 2 , . Replacement of the chloride with an iodide atom was performed with the use of excess NaI at elevated temperatures (70 °C) to produce iodinated adduct 3 .…”

Section: Resultsmentioning

confidence: 99%

“…In addition, it has been shown that 2′-deoxyinosine is capable of forming stable base pairs with all four DNA bases as assessed by UV thermal denaturation experiments with the stability of the base pairs having the following order of I−C > I−A > I−T > I−G – . Reactions that alkylate specifically at the N 3 position of thymidine and N 1 position of 2′-deoxyinosine , have been shown to proceed in high yield.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Wilds

Noronha

2008

Chem. Res. Toxicol.

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Interstrand cross-links, which are generated by chemotherapeutic treatment with bis-alkylating agents, exert their therapeutic effect by connecting the nucleobases of adjacent DNA strands together and represent some of the most threatening forms of damage suffered by genomic DNA. However, one of the reasons for treatment failure using these agents is due to enhanced repair of this DNA damage. The pursuit of understanding the repair of interstrand cross-links by repair systems has necessitated the synthesis of sufficient quantities of such damaged DNA. We report the synthesis of a site-specific interstrand cross-linked duplex containing an ethylene-bridged N (1)-2'-deoxyinosine- N (3)-thymidine base pair prepared by solution and solid-phase synthesis as a mimic for the lesion formed by the therapeutic agent 1,3-bis-(2-chloroethyl)-1-nitrosourea using both a phosphoramidite and a bis-phosphoramidite approach. UV thermal denaturation experiments revealed that this cross-linked duplex was stabilized by 52 degrees C relative to the noncross-linked control, and circular dichroism studies indicated little deviation from a B-form structure compared to a duplex that contained a G-C base pair at the same position. Molecular models of the cross-linked duplex that were geometry optimized using the AMBER forcefield also suggest that this lesion induces minimal distortion in B-form DNA. This modified oligonucleotide will be useful for studies related to the investigation of interstrand cross-linked DNA repair.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Wilds

Noronha

2008

Chem. Res. Toxicol.

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“…[12,13] We took advantage of this reactivity for the synthesis of 6-oxo-M 1 dG by alkylating dG with commercially available ethyl cis-3-bromoacrylate (K 2 CO 3 , DMF) through an addition-elimination pathway to afford N1-(3-carboxyethyl-1-propenyl)-dG (Scheme 2). [5] Subsequent treatment with sodium methoxide in methanol provided 6-oxo-M 1 dG.…”

Section: Resultsmentioning

confidence: 99%

“One-Pot” Syntheses of Malondialdehyde Adducts of Nucleosides

Székely

Wang

Peplowski

et al. 2008

Nucleosides, Nucleotides and Nucleic Acids

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“…To prepare the key intermediate, TBDMS-protected 20 (Scheme 2), we examined the reaction of 17 (26) with 18 in THF in the presence of the mild base Cs 2 CO 3 (27). This reaction gave only one significant product, the 1-(2′′,3′′-diacetoxypropyl) substitution product 19, in excellent yield (84%).…”

Section: Resultsmentioning

confidence: 99%

Regioselective Synthesis of 1,N²-Etheno-2‘-Deoxyguanosine and Its Generation in Oligomeric DNA

Huang

Torres

Iden

et al. 2003

Chem. Res. Toxicol.

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Chloroethylene oxide and chloroacetaldehyde, reactive intermediates derived from vinyl chloride, and the epoxy-hydroxy-alkanals, produced endogenously in the metabolism of polyunsaturated fatty acids, react with nucleic acid bases in DNA to form exocyclic etheno derivatives of 2'-deoxyadenosine, 2'-deoxyguanosine, and 2'-deoxycytidine. This paper describes an efficient method for the synthesis of the exocyclic 1,N(2)-etheno adduct of 2'-deoxyguanosine and its incorporation into DNA oligomers using automated synthesis techniques. The synthesis was initiated by a high-yield alkylation of N(2)-protected 2'-deoxyguanosine at the 1-position with 1,2-diacetoxy-3-bromopropane. The product was converted to the 5'-O-dimethoxytrityl-3'-O-phosphoramidite using published techniques and incorporated site specifically into DNA oligomers with 99% coupling efficiency. Ring closure to yield the 6-hydroxyethano derivative was accomplished by oxidation with sodium periodate, and facile dehydration then afforded DNA oligomers containing 1,N(2)-etheno-2'-deoxyguanosine. All oligomers were characterized fully by physicochemical methods.

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Regioselective 1‐Alkylation of 2′‐Deoxyguanosine.

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 5 publications

References 1 publication

Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

“One-Pot” Syntheses of Malondialdehyde Adducts of Nucleosides

Regioselective Synthesis of 1,N²-Etheno-2‘-Deoxyguanosine and Its Generation in Oligomeric DNA

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Regioselective 1‐Alkylation of 2′‐Deoxyguanosine.

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 5 publications

References 1 publication

Synthesis and Characterization of DNA Containing anN1-2′-Deoxyinosine-ethyl-N3-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Synthesis and Characterization of DNA Containing anN1-2′-Deoxyinosine-ethyl-N3-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

“One-Pot” Syntheses of Malondialdehyde Adducts of Nucleosides

Regioselective Synthesis of 1,N2-Etheno-2‘-Deoxyguanosine and Its Generation in Oligomeric DNA

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Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Synthesis and Characterization of DNA Containing anN¹-2′-Deoxyinosine-ethyl-N³-thymidine Interstrand Cross-Link: A Structural Mimic of the Cross-Link Formed by 1,3-Bis-(2-chloroethyl)-1-nitrosourea

Regioselective Synthesis of 1,N²-Etheno-2‘-Deoxyguanosine and Its Generation in Oligomeric DNA