Nucleotides, Part LXI, Phthaloyl Strategy: A New Concept of Oligonucleotide Synthesis

Beier, Markus; Pfleiderer, Wolfgang

doi:10.1002/(sici)1522-2675(19990407)82:4<633::aid-hlca633>3.0.co;2-u

Cited by 12 publications

(11 citation statements)

References 16 publications

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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 ].…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…For the full protection of the cytosine and adenine residues, the phthaloyl group was utilized [ 26 , 27 , 28 , 29 , 30 ]. This protecting group enabled us to protect the two protons of the amino group of the C or A base simultaneously via formation of a five-membered ring.…”

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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“…In order to eliminate the interaction of the difluorocarbene with the 6- N -benzoyl protecting group, we tested 6- N -phthaloyl protection [22] for the exo amino group in the adenine ring, since a phthaloyl strategy for the protection of an amino group had previously been used for the reaction with TFDA [14]. Thus, treatment of 20b [prepared (76%) by reaction of 9-(2,3- O -isopropylidene-5-deoxy-β-D- erythro -pent-4-enofuranosyl)adenine [23] 20a with phthaloyl dichloride in pyridine] with TFDA followed by column chromatography afforded 21a and 21b in 11% and 6% yield, respectively (Scheme 8).…”

Section: Resultsmentioning

confidence: 99%

“…BzCl (36 µL, 44 mg, 0.31 mmol) was added to a stirred solution of 2',3'- O -isopropylidene-6- N -phthaloyladenosine [29] ( 22a , 120 mg, 0.27 mmol; prepared by standard protection of 6- N -phthaloyladenosine [22] with acetone) in pyridine (3 mL) at 0 °C. After 16 h, the volatiles were evaporated and the residue was partitioned (1N HCl/H 2 O//CHCl 3 ).…”

Section: Methodsmentioning

confidence: 99%

Reactions of trimethylsilyl fluorosulfonyldifluoroacetate with purine and pyrimidine nucleosides

Rapp

Cai

Xü

et al. 2009

Journal of Fluorine Chemistry

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Difluorocarbene, generated from trimethylsilyl fluorosulfonyldifluoroacetate (TFDA), reacts with the uridine and adenosine substrates preferentially at the enolizable amide moiety of the uracil ring and the 6-amino group of the purine ring. 2',3'-Di-O-acetyl-3'-deoxy-3'-methyleneuridine reacts with TFDA to produce 4-O-difluoromethyl product derived from an insertion of difluorocarbene into the 4-hydroxyl group of the enolizable uracil ring. Reaction of the difluorocarbene with the adenosine substrates having the unprotected 6-amino group in the purine ring produced the 6-N-difluoromethyl derivative, while reaction with 6-N-benzoyl protected adenosine analogues gave the difluoromethyl ether product derived from the insertion of difluorocarbene into the enol form of the 6-benzamido group. Treatment of the 6-N-phthaloyl protected adenosine analogues with TFDA resulted in the unexpected one-pot conversion of the imidazole ring of the purine into the corresponding N-difluoromethylthiourea derivatives. Treatment of the suitably protected pyrimidine and purine nucleosides bearing an exomethylene group at carbons 2', 3' or 4' of the sugar rings with TFDA afforded the corresponding spirodifluorocyclopropyl analogues but in low yields.

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“…Thus, direct phthaloylamination of 3′,5′‐ O ‐(1,1,3,3‐tetraisopropyldisiloxy)‐1′‐deoxy‐1′‐(2,4‐difluorophenyl)‐2′‐( β‐ hydroxyethyl)‐ β ‐ D ‐ribofuranose ( 11 ) under Mitsunobu conditions17 with diethylazodicarboxylate (DEAD), triphenylphosphine and phthalimide afforded the phthalimide‐protected nucleoside 20 in excellent yield (79 %). The advantage of this synthetic strategy is the orthogonality of the phthalimide and dimethoxytrityl protecting groups, which means that the phthalimide group can be used in solid‐phase oligoribonucleotide synthesis 18. This group is stable under the standard phosphoroamidite coupling conditions and can be cleaved simultaneously with the exocyclic amino protecting groups of the natural nucleobases in NH 3 /MeOH (3:1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2′‐Aminoalkyl‐Substituted Fluorinated Nucleobases and Their Influence on the Kinetic Properties of Hammerhead Ribozymes

Klöpffer

Engels

2004

ChemBioChem

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Hammerhead ribozymes are ribonucleic acids that catalyse the hydrolytic cleavage of RNA. They interfere with gene expression in a highly specific manner and recognize the mRNA target through Watson-Crick base pairing. To overcome the problem of point mutations (Watson-Crick "mismatches") occurring in viral genomes, we developed 2'-aminoethyl-substituted fluorinated nucleosides, which are universal nucleobases. The highly efficient synthetic pathway, which features a direct phthaloylamination of a primary alcohol under Mitsunobu conditions, leads to modified phosphoroamidites. The 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-2'-(beta-aminoethyl)-beta-D-ribofuranose nucleoside analogue does not differentiate between the four natural nucleosides and leads to a RNA duplex that is as stable as the unmodified parent duplex. Upon incorporation into a ribozyme, the analogue's catalytic activity is equal for all four possible substrates, and the cleavage rates for the modified ribozymes are significantly higher (up to a factor of 13) than for the natural Watson-Crick "mismatch" base pairs. In agreement with the thermodynamic data obtained by measurement of the T(m) values of the RNA 12-mers, the cleavage rates for the 2'-substituted fluorinated benzimidazole derivative 4 are slightly higher than for the corresponding fluorinated benzene derivative 3.

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Nucleotides, Part LXI, Phthaloyl Strategy: A New Concept of Oligonucleotide Synthesis

Cited by 12 publications

References 16 publications

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

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

Reactions of trimethylsilyl fluorosulfonyldifluoroacetate with purine and pyrimidine nucleosides

Synthesis of 2′‐Aminoalkyl‐Substituted Fluorinated Nucleobases and Their Influence on the Kinetic Properties of Hammerhead Ribozymes

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