4546-72-9Relevant academic research and scientific papers
Base-base recognition of nonionic dinucleotide analogues in an apolar environment studied by low-temperature NMR spectroscopy
Xiao, Zhou,Weisz, Klaus
scheme or table, p. 3862 - 3869 (2010/05/15)
Two self-complementary dinucleotide analogues TSiA and A si with a nonionic diisopropylsilyl-modified backbone were synthesized, and their association in a nonaqueous aprotic environment was studied by NMR spectroscopy. Using a CDClF2/CDF3 solvent mixture, measurements at temperatures as low as 113 K allowed the observation and structural characterization of individual complexes in the slow exchange regime. The AsiT analogue associates to exclusively form a dinucleotide antiparallel duplex with regular Watson-Crick base pairing, but both A and T nucleosides exhibit a predominant C3'-endo sugar pucker reminiscent of an A-type conformation. In contrast to AsiT the TSiA dinucleotide is found to exhibit significant variability and flexibility. Thus, different secondary structures with weaker hydrogen bonds for all T SiA structures are observed at low temperatures. Although a B-like Watson-Crick antiparallel dinucleotide duplex with a preferred C2'-endo sugar pucker largely predominates at temperatures above 153 K, two additional species, namely a dinucleotide Hoogsteen duplex with a syn glycosidic torsion angle of the adenosine nucleoside and a presumably intramoleculariy folded structure, are increasingly populated upon further cooling. By adding typical DNA intercalators like anthracene or benz[c]acridine derivatives to the A siT dinucleotide duplex in the aprotic solvent environment, no binding of the polycyclic aromatic molecules can be detected even at lower temperatures. Obviously, van der Waals and stacking interactions are insufficient to compensate for the other unfavorable contributions to the overall free energy of binding, and only in the presence of additional hydrophobic effects in an aqueous environment does binding occur.
Intramolecular sensitization of photocleavage of the photolabile 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protecting group: Photoproducts and photokinetics of the release of nucleosides
Woell, Dominik,Smirnova, Julia,Galetskaya, Marina,Prykota, Tamara,Buehler, Jochen,Stengele, Klaus-Peter,Pfleiderer, Wolfgang,Steiner, Ulrich E.
experimental part, p. 6490 - 6497 (2009/09/06)
Novel photolabile protecting groups based on the 2-(2-nitrophenyl)- propoxycarbonyl (NPPOC) group with a covalently linked thioxanthone as an intramolecular triplet sensitizer exhibit significantly enhanced light sensitivity under continuous illumination. Herein we present a detailed study of the photokinetics and photoproducts of nucleosides caged with these new protecting groups. Relative to the parent NPPOC group, the light sensitivity of the new photolabile protecting groups is enhanced by up to a factor of 21 at 366 nm and is still quite high at 405 nm, the wavelength at which the sensitivity of the parent compound is practically zero. A new pathway for de-protection of the NPPOC group pro_ceeding through a nitroso benzylalcohol intermediate has been discovered to complement the main mechanism, which involves β elimination. Under standard conditions of lithographic DNA-chip synthesis, some of the new compounds, while maintaining the same chip quality, react ten times faster than the unmodified NPPOC-protected nucleosides.
An enzymatic transglycosylation of purine bases
Roivainen, Jarkko,Elizarova, Tatiana,Lapinjoki, Seppo,Mikhailopulo, Igor A.,Esipov, Roman S.,Miroshnikov, Anatoly I.
, p. 905 - 909 (2008/09/17)
An enzymatic transglycosylation of purine heterocyclic bases employing readily available natural nucleosides or sugar-modified nucleosides as donors of the pentofuranose fragment and recombinant nucleoside phosphorylases as biocatalysts has been investigated. An efficient enzymatic method is suggested for the synthesis of purine nucleosides containing diverse substituents at the C6 and C2 carbon atoms. The glycosylation of N6-benzoyladenine and N2-acetylguanine and its O6-derivatives is not accompanied by deacylation of bases. Copyright Taylor & Francis Group, LLC.
Polymer supported carbodiimide strategy for the synthesis of N-acylated derivatives of deoxy- and ribo purinenucleosides using active esters
Tripathi, Snehlata,Misra, Krishna,Sanghvi, Yogesh S.
, p. 5045 - 5048 (2007/10/03)
A cost-effective synthetic strategy has been used for the selective protection of the exocyclic amino function of purine nucleosides. Instead of using the common protecting groups in their chloride or anhydride forms, the less expensive and nontoxic acidic form was chosen. The acids were first activated to an active ester form using DCC and further successfully used for N-acylation of purine nucleosides. The contamination of the N-acylated product with DCU was inconvenient and was avoided by use of polymer supported- carbodiimide that has the additional advantage of reusability.
An improved transient method for the synthesis of N-benzoylated nucleosides
Zhu, Xue-Feng,Williams Jr., Howard J.,Scott, A. Ian
, p. 1233 - 1243 (2007/10/03)
The Jones' transient method for the synthesis of N-benzoylated nucleosides is improved by reducing the amounts of chlorotrimethylsilane (TMSCl) and benzoyl chloride to nearly equivalent quantities. The easy work-up and high yields of products are the major advantages of this approach. Jones' method is further simplified by omitting the addition of ammonium hydroxide. The utility of this modification for the preparation of some useful protected nucleosides is also presented.
Microwave assisted high yielding preparation of N-protected 2′-deoxyribonucleosides useful for oligonucleotide synthesis
Rao,Kumar,Chauhan,Garg,Gupta
, p. 393 - 400 (2007/10/03)
A rapid and high yielding method for the synthesis of precursors of synthons for DNA synthesis, N-protected 2′-deoxyribonucleosides is described, which occur under mild conditions using microwave irradiation. The desired material, N-protected nucleosides, was obtained in 93-96% yield in few minutes. The final products were then characterized by H-NMR and MALDI-TOF and compared with the standard samples. The method is amenable to small to moderate scale of synthesis.
Building blocks for the solution phase synthesis of oligonucleotides: Regioselective hydrolysis of 3′,5′-di-O-levulinylnucleosides using an enzymatic approach
Garcia, Javier,Fernandez, Susana,Ferrero, Miguel,Sanghvi, Yogesh S.,Gotor, Vicente
, p. 4513 - 4519 (2007/10/03)
A short and convenient synthesis of 3′- and 5′-O-levulinyl-2′-deoxynucleosides has been developed from the corresponding 3′,5′-di-O-levulinyl derivatives by regioselective enzymatic hydrolysis, avoiding several tedious chemical protection/deprotection steps. Thus, Candida antartica lipase B (CAL-B) was found to selectively hydrolyze the 5′-levulinate esters, furnishing 3′-O-levulinyl-2′-deoxynucleosides 3 in >80% isolated yields. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) and Candida antarctica lipase A (CAL-A) exhibit the opposite selectivity toward the hydrolysis at the 3′-position, affording 5′-O-levulinyl derivatives 4 in >70% yields. A similar hydrolysis procedure was successfully extended to the synthesis of 3′- and 5′-O-levulinyl-protected 2′-O-alkylribonucleosides 7 and 8. This work demonstrates for the first time application of commercial CAL-B and PSL-C toward regioselective hydrolysis of levulinyl esters with excellent selectivity and yields. It is noteworthy that protected cytidine and adenosine base derivatives were not adequate substrates for the enzymatic hydrolysis with CAL-B, whereas PSL-C was able to accommodate protected bases during selective hydrolysis. In addition, we report an improved synthesis of dilevulinyl esters using a polymer-bound carbodiimide as a replacement for dicyclohexylcarbodiimide (DCC), thus considerably simplifying the workup for esterification reactions.
A facile method for deprotection of trityl ethers using column chromatography
Pathak, Ashish K.,Pathak, Vibha,Seitz, Lainne E.,Tiwari, Kamal N.,Akhtar, Mohammad S.,Reynolds, Robert C
, p. 7755 - 7757 (2007/10/03)
A mild, efficient and inexpensive detritylation method is reported that uses trifluoroacetic acid on a silica gel column to obtain pure, detritylated compounds in one-step. This method is applicable to acid stable as well as acid sensitive compounds with only slight alterations in the procedure. Nineteen examples are given.
The H-phosphonate approach to the synthesis of oligonucleotides and their phosphorothioate analogues in solution
Reese, Colin B.,Quanlai, Song
, p. 1477 - 1486 (2007/10/03)
A new approach to the synthesis of oligonucleotides and oligonucleotide phosphorothioates in solution is described; it is based on H-phosphonate coupling [with bis(2-chlorophenyl) phosphorochloridate 22 as the coupling agent] at -40 deg C, followed by in situ sulfur transfer involving either 2-(4-chlorophenylsulfanyl)isoindole-1,3(2H)-dione 23a or 4-[(2-cyanoethyl)sulfanyl]morpholine-3,5-dione 26. The yields of the coupling and sulfur transfer reactions are virtually quantitative and, following unblocking by previously reported procedures, very pure products (d[ApC], d[TpGpApC], d[TpGp(s)ApC], d[Gp(s)A] and d[Cp(s)Tp(s)Gp(s)A]) are obtained.
The S-pixyl group: An efficient photocleavable protecting group for the 5' hydroxy function of deoxyribonucleosides
Coleman, Michael P.,Boyd, Mary K.
, p. 7911 - 7915 (2007/10/03)
The 9-phenylthioxanthyl (S-pixyl or S-Px) group has been investigated as a photocleavable protecting group for primary alcohols, and specifically as a 5' hydroxy protecting group for deoxyribonucleosides. Several alcohols, including the four nucleosides with protected exocyclic amino functions, were protected in very good to excellent yield by treatment of 9-chloro-9-phenylthioxanthene 3 in dry pyridine to reveal the derivatized compounds. Irradiation of the protected substrates in neutral, aqueous solution regenerated the starting alcohols in excellent yield.
