Synthesis of oligonucleotides containing bulky adducts at guanine N2 via the phosphoramidite of O2-triflate-O6-NPE 2′-deoxyxanthosine (original) (raw)
Synthesis of oligodeoxynucleotides containing 6-N-([13C]methyl)adenine and 2-N-([13C]methyl)guanine
J Chem Soc Perkin Trans 1, 1997
Oligonucleotides containing 6-N-([ 13 C]methyl)adenine and 2-N-([ 13 C]methyl)guanine have been prepared for NMR studies using the deprotection step to introduce the [ 13 C]methylamine group. For this purpose, the use of 2'-deoxy-6-O-(pentafluorophenyl)inosine 1 and 2'deoxy-2-fluoro-6-O-[2-(4-nitrophenyl)-ethyl]inosine 2 as precursors of the N-methylated nucleosides is described. Preliminary NMR characterization of the 13 C-labelled oligonucleotides shows that the 13 C chemical shift of the methyl group in N-methylguanine is sensitive to duplex formation, making it a useful local probe.
Tetrahedron, 2006
A general and convenient method for synthesis of modified oligonucleotides by use of new non-nucleoside phosphoramidites is reported. A chiral 1,3-diol backbone of the modifying reagents is generated either from (R)-(+)-a-hydroxy-g-butyrolactone or (R)-(À)pantolactone. Aliphatic amines were acylated with the lactones to give the corresponding N-substituted 2,4-dihydroxybutyramides. After protection of a side chain, if necessary, the diols were converted into phosphoramidites or solid supports suitable for use in oligonucleotide synthesis. The reagents allow single, multiple or combined introduction of various functions (e.g., alkylamine, imidazole and pyrene residues) into synthetic oligonucleotides. The structures of the conjugates were confirmed by MALDI-TOF mass spectrometry.
Chem. Res. …, 2001
Butadiene is a major industrial chemical whose genotoxic effects are attributed to the reaction of its oxidized metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), with DNA. Nucleosides and oligonucleotides containing regio-and stereochemically specific adducts of BDO and the BDO2-related compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine [(2R)-and (2S)-N 2-(1-hydroxy-3-buten-2-yl) and (2R,3R)-and (2S,3S)-N 2-(2,3,4-trihydroxybut-1-yl), respectively] and on adenine [(2R)-and (2S)-N 6-(1-hydroxy-3-buten-2-yl) and (2R,3R)and (2S,3S)-N 6-(2,3,4-trihydroxybut-1-yl), respectively] have been prepared by nonbiomimetic routes. For guanine adducts, 2-fluoro-O 6-(trimethylsilylethyl)-2′-deoxyinosine was treated with (2R)-and (2S)-2-amino-3-buten-1-ol to give the BDO adducts and with (2R,3R)-and (2S,3S)-1-amino-2,3,4-butanetriol to produce the BDE adducts; the adducted oligonucleotides were prepared from 11-mer oligonucleotides containing the halopurine. Adenine adducts were prepared in a similar fashion using 6-chloropurine 2′-deoxyriboside as the reactive purine component.
The Journal of Organic Chemistry, 1995
The preparation of oligonucleotides containing 2-aza-2'-deoxyinosine is described. Protection of the 2-azahypoxanthine moiety with the photolabile 2-nitrobenzyl group enabled us to obtain the phosphoramidite derivative and oligonucleotides containing protected 2-aza-2'-deoxyinosine. After purification, photolysis of the oligonucleotides containing the protected analogue provided the desired oligonucleotides in good yields. Melting curves of duplexes containing 2-azahypoxanthine paired with the four natural bases at pH 6 and pH 8 proved that 2-azahypoxanthine base pairs were less stable than perfectly matched duplexes but showed little variation among different bases. Synthetic oligonucleotide probes have proven to be very useful in the detection of cloned DNA sequences. When a partial protein sequence is available, the design of oligonucleotide probes is complicated by the degeneracy of the genetic code. To circumvent this problem, a sustained effort has been devoted to the design of base analogues that can potentially base pair with any of the four natural bases. 2'-Deoxyinosine was the first compound studied and it is the most used.' Its ribonucleoside derivative, inosine, was found in &RNA at the third position of the anticodon, capable of pairing with the A, C, and U bases of the codon. Abasic and phenyl analogues have been prepared but base pairing was significantly less stable than the normal Watson-Crick base pairing.2 The preparation of oligonucleotides containing 2'-deoxyinosine derivatives: allopurinol 2'-deoxyriboside and 7-deaza-2'-deoxyinosine have also been de~cribed.~ Oligonucleotides containing 5-fluorouracil have been reported to form stable base pairs with adenine and guanine.4 Similarly, it has been shown that oligonucleotides containing pyrimidine analogues that have an amino-imino tautomeric constant near unity, pair equally well with A and G. The same holds for a purine analogue that is able to form strong base pairs with T and C.5 Very recently, oligonucleotides containing 3-nitropyrrole 2'-deoxyriboside at several sites have been used as primers for sequencing and polymerase chain reaction + Centro de Investigaci6n y Desarrolo.
Phosphotriester approach to the synthesis of oligonucleotides: a reappraisal
Journal of the Chemical Society, Perkin Transactions 1, 1993
The phosphotriester approach to the synthesis of oligodeoxyribo-and oligoribo-nucleotides in solution has been reinvestigated. The efficacy of mesitylene-2-sulfonyl chloride (MSCI) 15a, 2,4,6triisopropylbenzenesulfonyl chloride (TrisCI) 1 5b, 4bromobenzenesulfonyl chloride 1 5c. naphthalene-1-sulfonyl chloride 39, and 2-and 4-nitrobenzenesulfonyl chlorides 40a and 40b, respectively, as activating agents has been examined. The latter arenesulfonyl chlorides have been used in conjunction with the following nucleophilic catalysts: 1-methylimidazole, 3-nitro-I H-1,2,4-triazole 19, 5-(3-nitrophenyl)-l H-tetrazole 20a, 5-(3.5-dinitrophenyl)-l H-tetrazole 20b. 5-(1-methylimidazol-2y l)-I H-tetrazole 21, 5-[ (1-methylimidazol-2-yl)methyl]-1 H-tetrazole 22, 4-ethoxypyridine 1-oxide 14a. 4,6-dinitro-l-hydroxybenzotriazole 29a, 1-hydroxy-4-nitro-6-(trifluoromethyl) benzotriazole 29b. 1-hydroxy-5-phenyltetrazole 30a and 1-hydroxy-5-(3-nitrophenyl) tetrazole 30b. The rates of formation and yields of the fully protected dideoxyribonucleoside and diribonucleoside phosphates 37 and 47, respectively, were determined using various combinations of activating agents and nucleophilic catalysts. Although 2-and 4-nitrobenzenesulfonyl chlorides 40a and 40b. respectively, proved to be the most powerful activating agents, their use in the deoxy-series led to the formation of by-products and hence to unsatisfactory isolated yields of the dideoxyribonucleoside phosphate 37. I I +-0 ii. iii /o 3 4 Ar = 2-chlorophenyl; B and B' are protected in substrates 1, 2 and 3, and unprotected base residues in product 4
Tetrahedron Letters, 1999
Two oligonucleotidcs, partially modified with N,N-dimethylaminoethyl phosphoramidate groups, were obtained by an optimized solid-phase synthesis cycle based on H-phosphonate chemistry. Their use as third strands in parallel triple helices was shown to produce a decrease in stability with respect to all-phosphodiester otigonucleotide complexes, most probably due to unfavourable steric cftizcts. Phosphoramidate-modified oligonucleotides were shown to be notably stable to exonucleases.