Transient protection. 2. One-flask synthesis of 6-O-[(4-nitrophenyl)ethyl]-2'-deoxyguanosine nucleosides

Gao, Xiaolian; Gaffney, Barbara L.; Hadden, S. K.; Jones, R. A. C.

doi:10.1021/jo00355a038

Cited by 26 publications

(23 citation statements)

References 2 publications

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“…However, in oligoribonucleotide synthesis more moderate conditions are required because the 2'-hydroxyl positions are still protected. In our previous solidphase syntheses (1-2, 7) the oligoribonucleotides were de-acylated using the less severe conditions of 3:1 ammonium hydroxide-ethanol (550, [16][17][18] conditions. The problem of silyl group cleavage under severe ammonium hydroxide conditions can best be investigated using oligouridylic acid sequences since no exocyclic amino protecting groups are present.…”

Section: Resultsmentioning

confidence: 99%

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Prevention of chain cleavage in the chemical synthesis of 2′-silylated oligoribonucleotides

Wu¹,

1989

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Strong aqueous ammonium hydroxide used to remove N-acyl protecting groups from synthetic oligoribonucleotides causes removal of some alkylsilyl protecting groups from 2'-hydroxyls and leads to chain cleavage. This problem is most severe when 30% ammonium hydroxide is used and substantially reduced but still detectable when 3:1 ammonium hydroxide-ethanol is used. We have virtually eliminated this unwanted cleavage by incorporating the labile phenoxyacetyl amino protecting group on adenosine and guanosine. The N-benzoyl protecting group remains adequate for cytidine nucleosides. Synthetic oligoribonucleotides containing these N-acylated nucleosides and 2'-t-butyldimethylsilyl or 2'-triisopropylsilyl protecting groups can be deacylated by room temperature treatment in saturated anhydrous methanolic ammonia (8-12 h) without causing any detectable chain cleavage.

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Section: Resultsmentioning

confidence: 99%

“…al. (17) using trimethylsilyl chloride was used to block the hydroxyl positions of adenosine. Acylation was then performed using phenoxyacetic anhydride, prepared as previously described (11,18).…”

Section: Resultsmentioning

confidence: 99%

Prevention of chain cleavage in the chemical synthesis of 2′-silylated oligoribonucleotides

Wu¹,

1989

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“…Solvents was removed by evaporation, an additional 50 mL of H 2 O was added, and the solution was concentrated to induce N 2 ,3',5'-triacetyl-2'-deoxyguanosine crystal. 340 mg (0.87 mmol) of N 2 ,3',5'-triacetyl-2'-deoxyguanosine was dissolved in 2mL of dry dioxane and reacted with 450 mg (3.3 mmol) of triphenylphosphine, 500 μL (3.2 mmol) of diethylazodicarboxylate, and 212 μL (3.5 mmol) of 2-fluoroethanol at room temperature [17]. After 2 h, 20 mL of 5% NaHCO 3 solution was added.…”

Section: Methodsmentioning

confidence: 99%

Structural Characterization of the DNA Adducts Induced by 1,3-Bis-(2-Chloroethyl)-1-Nitrosourea Using Electrospray Ionization Tandem Mass Spectrometry

Bai

Zhao

Zhong

2010

2010 4th International Conference on Bioinformatics and Biomedical Engineering

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Bifunctional alkylating agent 1,3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) is a significant anticancer drug in the clinical treatment of human malignancies. A serious complication of treatment with BCNU is the increased risk of a secondary leukaemia in long-term survivors because not all alkylating agent interactions with DNA result in cell death. In the present work, high-performance liquid chromatography (HPLC) was combined with electrospray ionization tandem mass spectrometry (ESI-MS/MS) to develop a sensitive and selective method for the measurement of DNA adducts induced by BCNU. Double strand calf thymus DNA was treated with BCNU and digested enzymatically down to the nucleoside level. The hydrolysates were analyzed by HPLC separation followed by electrospray ionization tandem mass spectrometry. The main alkylated products, N 7 -(2-hydroxyethyl)deoxyguanosine (N 7 -HOEtdG), N 7 -(2-chloroethyl)deoxyguanosine (N 7 -ClEtdG) and 1-[N 3 -deoxycytidyl]-2-[N 1 -deoxyguanosyl]ethane (dG-dC) were qualitatively detected and quantitatively characterized by selected reaction monitoring (SRM) mode.

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“…The 2'-deoxyadenosine (14) reacted, after transient silylation, to N 6 -[(2-cyanoethoxy)carbonyl]-2'-deoxyadenosine (19), whereas 2'-deoxyguanosine (15) expectedly caused problems for solubility reasons, to give only 19% of N 2 -[2-(cyanoethoxy)carbonyl]-2'-deoxyguanosine (20), and starting from 3',5'-bis-O-[(tert-butyl)dimethylsilyl)]-2'-deoxyguanosine (16), to form 21 in 22% yield. Monotritylation of 18 and 19 gave the 5'-protected derivatives 22 and 23, respectively.…”

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confidence: 99%

“…Also an attempted alkylation with 3-iodopropanenitrile did not proceed in the anticipated manner. Finally, the method of Jones and co-workers [14] [15] was applied, converting 16 by 2,4,6-triisopropylbenzenesulfonyl chloride in the presence of Et 3 N and N,N-dimethylpyridin-4-amine (DMAP) to 3',5'-bis-O-[(tertbutyl)dimethylsilyl]-2'-deoxy-O 6 -[(2,4,6-triisopropylphenyl)sulfonyl]guanosine (24), which reacted with 3-hydroxypropanenitrile in presence of Et 3 N in a DABCOcatalyzed reaction to 3',…”

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confidence: 99%

Nucleotides, Part LXVII, The 2-Cyanoethyl and (2-Cyanoethoxy)carbonyl Group for Base Protection in Nucleoside and Nucleotide Chemistry

Merk¹,

Reiner²,

Kvasyuk³

et al. 2000

HCA

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The amino functions of the common 2'-deoxyribo-and ribonucleosides were blocked by the (2-cyanoethoxy)carbonyl group on treatment with 2-cyanoethyl carbonochloridate (5) or 1-[(2-cyanoethoxy)carbonyl]-3-methyl-1H-imidazolium chloride (6) leading to 7, 18, 8, 19, 9, and 20. In 2'-deoxyguanosine, the amide group was additionally blocked at the O 6 position by the 2-cyanoethyl ( 3 27) and 2-(4-nitrophenyl)ethyl group ( 3 31, 32). Comparative kinetic studies regarding the cleavage of the ce/ceoc and npe/npeoc group by b-elimination revealed valuable information about the ease and sequential deprotection of the various blocking groups at different sites of the nucleobases. Besides the 5'guanosine analog 40 is recommended as building block for oligo-2'-deoxyribonucleotide synthesis. Introduction. ± The development of the 2-(4-nitrophenyl)ethyl (npe) and [2-(4-nitrophenyl)ethoxy]carbonyl (npeoc) groups as versatile protective groups for nucleobases [2], phosphate [3] [4], and phosphite functions [5] [6] broadened the strategy of nucleoside and nucleotide protection in oligonucleotide synthesis universally. The great advantange of these groups is their high stability under acidic and mild basic hydrolytic conditions as, for example, in the presence of ammonia and amines in MeOH, dioxane, or H 2 O, whereas their cleavage can easily and quantitatively be achieved by 1,8-diazabicyclo[5.4.0]undecene (DBU) in aprotic solvents by a b-elimination process.The 2-cyanoethyl (ce) group [7] [8] is the most common blocking group for the phosphate and phosphite moiety of nucleotides, but strangely enough, the ce and its corresponding (2-cyanoethoxy)carbonyl (ceoc) group have not been applied for base protection in analogy to the npe/npeoc couple. Several years ago, we [9] [10] developed the ce/ceoc strategy as an alternative approach for the synthesis of special oligonucleotides. Details about the nucleobase protection by the ce and ceoc group will now be reported since N-{[(2-cyanoethoxy)carbonyl]oxy}succinimide has recently been described as a new reagent for protection of amino groups in oligonucleotides [11]. We protected the amino group in cytidine, adenosine, and guanosine as well as in the corresponding 2'-deoxynucleosides with the ceoc group and utilized the ce group

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Transient protection. 2. One-flask synthesis of 6-O-[(4-nitrophenyl)ethyl]-2'-deoxyguanosine nucleosides

Abstract: Transient protection of both the 3'-and 5'-hydroxyl groups of la or of the 3'-hydroxyl group of lb, followed

Cited by 26 publications

References 2 publications

Prevention of chain cleavage in the chemical synthesis of 2′-silylated oligoribonucleotides

Prevention of chain cleavage in the chemical synthesis of 2′-silylated oligoribonucleotides

Structural Characterization of the DNA Adducts Induced by 1,3-Bis-(2-Chloroethyl)-1-Nitrosourea Using Electrospray Ionization Tandem Mass Spectrometry

Nucleotides, Part LXVII, The 2-Cyanoethyl and (2-Cyanoethoxy)carbonyl Group for Base Protection in Nucleoside and Nucleotide Chemistry

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