An Improved Method for the Synthesis of<i>N</i>
                  <sup>3</sup>-Benzoylthymidine

Sekine, Mitsuo; Fujii, Mitsuo; Nagai, Hisashi; Hata, Tsujiaki

doi:10.1055/s-1987-28192

Cited by 23 publications

(11 citation statements)

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“…All reagents and anhydrous solvents were obtained from Aldrich, except for the following: 20% w/v phosgene in toluene, from Fluka; thymidine, 2‘-deoxyinosine, N 2 -(phenoxyacetyl)-2‘-deoxyguanosine, N 2 -isobutyryl-2‘-deoxyguanosine, N 4 -isobutyryl-2‘-deoxycytidine, N 6 -(phenoxyacetyl)-2‘-deoxyadenosine, and diisopropylammonium tetrazolide, from Chem-Impex (Wood Dale, IL); 2-(cyanoethyl)- N , N , N ‘, N ‘-tetraisopropylphosphorodiamidite, from ChemGenes (Waltham, MA); fluorescein phosphoramidite (Fluoreprime) and 5‘-DMT-2‘-deoxynucleoside 3‘-phosphoramidites, from Pharmacia Biotech; DNA synthesis reagents and anhydrous acetonitrile from Glen Research (Sterling, VA); silica gel (60 Å pore size, 230−400 mesh for flash chromatography), E. Merck. N 3 -Benzoylthymidine was prepared as previously described and O 6 -( N , N -diphenylcarbamoyl)- N 2 -(phenoxyacetyl)-2‘-deoxyguanosine (dpc/pac-dG) were prepared using modifications of reported methods which are available as Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

McGall¹,

Barone²,

Diggelmann³

et al. 1997

J. Am. Chem. Soc.

281

239

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New methods based on photolithography and surface fluorescence were used to determine photodeprotection rates and stepwise yields for light-directed oligonucleotide synthesis using photolabile 5‘-(((α-methyl-2-nitropiperonyl)oxy)carbonyl)(MeNPOC)-2‘-deoxynucleoside phosphoramidites on planar glass substrates. Under near-UV illumination (primarily 365 nm) from a mercury light source, the rate of photoremoval of the MeNPOC protecting group was found to be independent of both the nucleotide and length of the growing oligomer (t 1/2 = 12 s at 27.5 mW/cm2). A moderate dependence on solvent polarity was observed, with photolysis proceeding most rapidly in the presence of nonpolar solvents or in the absence of solvent (e.g., t 1/2 = 10−13 s at 27.5 mW/cm2). In solution, the photolysis rate was linearly dependent on light intensity over the range 5−50 mW/cm2. Average stepwise yields for the synthesis of dodecamer oligonucleotides were in the range of 92−94%, using monomers based on N 6-(phenoxyacetyl)-2‘-deoxyadenosine, N 2-isobutyryl-2‘-deoxyguanosine, N 4-isobutyryl-2‘-deoxycytidine, and thymidine. By comparison, an efficiency of 98%/step was obtained using a conventional 5‘-dimethoxytrityl monomer with acid deprotection on the same support. The lower yields associated with the photochemical process appears to be due to incomplete recovery of free 5‘-hydroxyl groups after photolysis on the support, although high yields of 5‘-OH nucleosides (≥96%) are consistently observed when 5‘-MeNPOC monomers are photolyzed in solution.

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Section: Methodsmentioning

confidence: 99%

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

McGall¹,

Barone²,

Diggelmann³

et al. 1997

J. Am. Chem. Soc.

281

239

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“…To evaluate the deactivation of the fully protected nucleobases towards cyanoethylation with acrylonitrile, we synthesized fully protected phosphoramidite units, as previously reported [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. The benzoyl group was selected as a full protecting group for the thymine residue [ 24 , 25 ]. The N 3 -protection of 2′-deoxythymidine by reaction with benzoyl chloride gave compound 2 quantitatively via the transient O -trimethylsilylation.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Oligodeoxynucleotides Using Fully Protected Deoxynucleoside 3′-Phosphoramidite Building Blocks and Base Recognition of Oligodeoxynucleotides Incorporating N3-Cyano-Ethylthymine

Tsunoda

Kudo²,

Ohkubo³

et al. 2010

Molecules

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Oligodeoxynucleotide (ODN) synthesis, which avoids the formation of side products, is of great importance to biochemistry-based technology development. One side reaction of ODN synthesis is the cyanoethylation of the nucleobases. We suppressed this reaction by synthesizing ODNs using fully protected deoxynucleoside 3′-phosphoramidite building blocks, where the remaining reactive nucleobase residues were completely protected with acyl-, diacyl-, and acyl-oxyethylene-type groups. The detailed analysis of cyanoethylation at the nucleobase site showed that N3-protection of the thymine base efficiently suppressed the Michael addition of acrylonitrile. An ODN incorporating N3-cyanoethylthymine was synthesized using the phosphoramidite method, and primer extension reactions involving this ODN template were examined. As a result, the modified thymine produced has been proven to serve as a chain terminator.

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“…The organic solubility of fully protected oligodeoxyribonucleotides might also be improved by the protection of thymidine residues via N 3 -acylation or the introduction of a second nucleobase protecting group on guanine residues …”

Section: Discussionmentioning

confidence: 99%

The Dimethoxytrityl Resin Product Anchored Sequential Synthesis Method (DMT PASS): A Conceptually Novel Approach to Oligonucleotide Synthesis

Mihaichuk

Hurley

Vagle

et al. 2000

Org. Process Res. Dev.

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Presented is a conceptually novel approach to oligonucleotide synthesis referred to herein as dimethoxytrityl resin product anchored sequential synthesis (DMT PASS). The DMT PASS process is characterized by the reaction of a 3‘-protected nucleoside or oligonucleotide with an excess of a nucleotide 3‘-phosphoramite or H-phosphonate which is bound to a dimethoxytrityl functionalized polystyrene resin. As a result, successfully coupled oligonucleotide product is then attached to the solid support, allowing for removal and potential recovery of starting materials. The protected oligonucleotide product is then released and subjected to an aqueous/organic extractive purification, which serves to remove monomeric impurities. The PASS process is anticipated to provide for the cost-effective manufacture of oligonucleotides on a scale which would allow for clinical development and pharmaceutical product commercialization. Herein we describe some aspects of our process development progress and discuss preliminary applications of the process to the synthesis of short oligodeoxyribonucleotide sequences, as well as a number of challenges confronting the PASS development effort.

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An Improved Method for the Synthesis ofN ³-Benzoylthymidine

Cited by 23 publications

References 0 publications

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

Synthesis of Oligodeoxynucleotides Using Fully Protected Deoxynucleoside 3′-Phosphoramidite Building Blocks and Base Recognition of Oligodeoxynucleotides Incorporating N3-Cyano-Ethylthymine

The Dimethoxytrityl Resin Product Anchored Sequential Synthesis Method (DMT PASS): A Conceptually Novel Approach to Oligonucleotide Synthesis

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An Improved Method for the Synthesis ofN 3-Benzoylthymidine

Cited by 23 publications

References 0 publications

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates

Synthesis of Oligodeoxynucleotides Using Fully Protected Deoxynucleoside 3′-Phosphoramidite Building Blocks and Base Recognition of Oligodeoxynucleotides Incorporating N3-Cyano-Ethylthymine

The Dimethoxytrityl Resin Product Anchored Sequential Synthesis Method (DMT PASS): A Conceptually Novel Approach to Oligonucleotide Synthesis

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An Improved Method for the Synthesis ofN ³-Benzoylthymidine