Chemoselective Deprotection of Triethylsilyl Ethers

Chandra, Tilak; Broderick, William E.; Broderick, Joan B.

doi:10.1080/15257770903362172

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…7b), and MS. In addition, the structures of these two closely related products were based on our recent report where we used 2D rotating-frame nuclear Overhauser effect spectroscopy and nuclear Overhauser effect spectroscopy of open and closed forms, as well as of the 5 R and 5 S dinucleosides, to confirm the stereochemistry [27, 37]. …”

Section: Resultsmentioning

confidence: 99%

Complete stereospecific repair of a synthetic dinucleotide spore photoproduct by spore photoproduct lyase

et al. 2010

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Spore photoproduct lyase (SP lyase), a member of the radical S-adenosylmethionine superfamily of enzymes, catalyzes the repair of 5-thyminyl-5,6-dihydrothymine [spore photoproduct (SP)], a type of UV-induced DNA damage unique to bacterial spores. The anaerobic purification and characterization of Clostridium acetobutylicum SP lyase heterologously expressed in Escherichia coli, and its catalytic activity in repairing stereochemically defined synthetic dinucleotide SPs was investigated. The purified enzyme contains between 2.3 and 3.1 iron atoms per protein. Electron paramagnetic resonance (EPR) spectroscopy reveals an isotropic signal centered at g = 1.99, characteristic of a [3Fe-4S] + cluster accounting for 3-4% of the iron in the sample. Upon reduction, a nearly axial signal (g = 2.03, 1.93 and 1.92) characteristic of a [4Fe-4S] + cluster is observed that accounts for 34-45% of total iron. Addition of S-adenosyl-methionine to the reduced enzyme produces a rhombic signal (g = 2.02, 1.93, 1.82) unique to the S-adenosyl-Lmethionine complex while decreasing the overall EPR intensity. This reduced enzyme is shown to rapidly and completely repair the 5R diastereomer of a synthetic dinucleotide SP with a specific activity of 7.1 ± 0.6 nmol min −1 mg −1 , whereas no repair was observed for the 5S diastereomer.

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Section: Resultsmentioning

confidence: 99%

Complete stereospecific repair of a synthetic dinucleotide spore photoproduct by spore photoproduct lyase

et al. 2010

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“…The coupling reaction between the enolate of 3 and bromomethyl deoxyuridine 2 afforded 4 and 5 (1.2:1.0) in 53% total yield. After separation via flash chromatography using a literature procedure, 55 the resulting 5 was treated with either 4% HF in pyridine 53 or HCO 2 H in methanol 55 to remove the triethylsilyl (TES) protecting groups, generating 6 . The yield of 6 is modest in either reaction due to the unexpected loss of the tert -butyldimethylsilyl (TBS) moiety.…”

Section: Resultsmentioning

confidence: 99%

Chemical Syntheses of Oligodeoxyribonucleotides Containing Spore Photoproduct

Jian

2013

J. Org. Chem.

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5-(α-Thyminyl)-5,6-dihydrothymine, also called spore photoproduct or SP, is commonly found in the genomic DNA of UV irradiated bacterial endospores. Despite the fact that SP was discovered nearly 50 years ago, its biochemical impact is still largely unclear due to the difficulty to prepare SP containing oligonucleotide in high purity. Here, we report the first synthesis of the phosphoramidite derivative of dinucleotide SP TpT, which enables successful incorporation of SP TpT into oligodeoxyribonucleotides with high efficiency via standard solid phase synthesis. This result provides the scientific community a reliable means to prepare SP containing oligonucleotides, laying the foundation for future SP biochemical studies. Thermal denaturation studies of the SP containing oligonucleotide found that SP destabilizes the duplex by 10–20 kJ/mole, suggesting that its presence in the spore genomic DNA may alter the DNA local conformation.

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“…[21,23] The 5 R and 5 S -diastereomers were purified on a silica gel column using a gradient of ethyl acetate and hexanes. The stereochemistry of protected dinucleosides was determined by two-dimensional Nuclear Overhauser Enhancement Spectroscopy (NOESY) and Rotating-frame Overhauser Effect Spectroscopy (ROESY).…”

Section: Resultsmentioning

confidence: 99%

“…[21] In the next step the tert -butyldimethylsilyl (TBDMS) and triethylsilyl (TES) groups were removed using HF:pyridine at room temperature in good yields to produce the di-SEM protected 5R ( 1 ) and 5S -dinucleosides ( 5 ). [23] …”

Section: Resultsmentioning

confidence: 99%

“…[21,22] Our need for pure SP substrate for mechanistic studies has led us to develop methods for the synthesis of stereochemically-defined dinucleoside and dinucleotide SP substrates. [21–23] The complete multistep synthesis of 5 R and 5 S -spore photoproducts from thymidine involves the condensation of dihydrothymidine and thymidine, selective deprotection of triethylsilyl groups, [23] phosphorylation at the 3′ hydroxyl of dihydrothymidine and phosphodiester bond formation between dihydrothymidine and thymidine. Only a few methods are reported for deprotecting the N -SEM from nucleosides and nucleotides; these proved unsatisfactory for the deprotection of N-SEM from SP dinucleosides and dinucleotides (Table 1), and led us to develop the alternate method described here.…”

Section: Introductionmentioning

confidence: 99%

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