The Experts below are selected from a list of 4971 Experts worldwide ranked by ideXlab platform
Joseph A. Piccirilli - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of 5 thio 3 o ribonucleoside Phosphoramidites
Journal of Organic Chemistry, 2017Co-Authors: Nansheng Li, Jun Lu, Joseph A. PiccirilliAbstract:The chemical synthesis of Phosphoramidite derivatives of all four 5′-deoxy-5′-thioribonucleosides is described. These Phosphoramidites contained trityl (A, G, C, and U), dimethoxytrityl (A and G), or tert-butyldisulfanyl (G) as the 5′-S-protecting group. The application of several of these Phosphoramidites for solid-phase synthesis of oligoribonucleotides containing a 2′-O-photocaged 5′-S-phosphorothiolate linkage or 5′-thiol-labeled RNAs is also further investigated.
-
Synthesis of 5′-Thio-3′‑O‑ribonucleoside Phosphoramidites
2017Co-Authors: Joseph A. PiccirilliAbstract:The chemical synthesis of Phosphoramidite derivatives of all four 5′-deoxy-5′-thioribonucleosides is described. These Phosphoramidites contained trityl (A, G, C, and U), dimethoxytrityl (A and G), or tert-butyldisulfanyl (G) as the 5′-S-protecting group. The application of several of these Phosphoramidites for solid-phase synthesis of oligoribonucleotides containing a 2′-O-photocaged 5′-S-phosphorothiolate linkage or 5′-thiol-labeled RNAs is also further investigated
-
Supplementary Data
2016Co-Authors: John K Frederiksen, David M J Lilley, Selene C. Koo, Timothy J. Wilson, Joseph A. PiccirilliAbstract:monomethoxytrityl-3´-mercaptothymidine with 3´-O-acetylthymidine in the presence of (tetrazol-1-yl)2POCH2CH2CN and 2,6-lutidine (1) d(T3´-ST) Solid phase synthesis using thymidine 3´-S-Phosphoramidite (2) d(GCACGT3´-STGCACG) Solid phase synthesis using thymidine 3´-S-Phosphoramidite Thio analog of a thymine photodimer (3) Metal ion-dependent cleavage by the Tetrahymena group I ribozyme (4) d(CCCUCU3´-SA) Solid phase synthesis using ribo- and deoxyribouridine 3´-S-Phosphoramidites Metal ion-dependent cleavage by Klenow fragment of E. coli DNA polymerase
-
synthesis of 2 c α hydroxyalkyl and 2 c α alkylcytidine Phosphoramidites analogues for probing solvent interactions with rna
Journal of Organic Chemistry, 2007Co-Authors: Joseph A. PiccirilliAbstract:Nucleoside analogues bearing 2‘-C-α-(hydroxyalkyl) and 2‘-C-α-alkyl substitutes have numerous applications in RNA chemistry and biology. In particular, they provide a strategy to probe the interaction between the 2‘-hydroxyl group of RNA and water. To incorporate these nucleoside analogues into oligonucleotides for studies of the group II intron (Gordon, P. M.; Fong, R.; Deb, S.; Li, N.-S.; Schwans, J. P.; Ye, J.-D.; Piccirilli, J. A. Chem. Biol. 2004, 11, 237), we synthesized six new Phosphoramidite derivatives of 2‘-deoxy-2‘-C-α-(hydroxyalkyl)cytidine (36: R = −(CH2)2OH; 38: R = −(CH2)3OH; 40: R = −(CH2)4OH) and 2‘-deoxy-2‘-C-α-alkylcytidine (37: R = −CH2CH3; 39: R = −(CH2)2CH3; 41: R = −(CH2)3CH3) from cytidine or uridine via 2‘-C-α-allylation, followed by alkene and alcohol transformations. Phosphoramidites 36 and 37 were prepared from cytidine in overall yields of 14% (10 steps) and 7% (11 steps), respectively. Phosphoramidites 38 and 39 were prepared from uridine in overall yields of 30% (10 s...
-
Synthesis of 3'-thioribonucleosides and their incorporation into oligoribonucleotides via Phosphoramidite chemistry.
RNA, 1997Co-Authors: A. Yoshida, Joseph A. PiccirilliAbstract:Oligoribonucleotides containing 3'-S-phosphorothiolate linkages are valuable probes in nucleic acid biochemistry, but their accessibility has been limited because 3'-thioribonucleoside Phosphoramidites have not been available. We synthesized 3'-thioribonucleoside derivatives (C, G, and U) via glycosylations of nucleoside bases with 3-S-thiobenzoyl-5-O-toluoyl-1,2-O-diacetylfuranose 5, which was obtained from 1 ,2-O-isopropylidene-5-O-toluoyl-3-trifluoromethane-sulfonyl-alpha-D-x ylofuranose 2 by SN2 displacement with sodium thiobenzoate. Additionally, a 3'-thioinosine derivative was prepared from inosine via direct modification of the ribose, analogous to the previously reported synthesis of 3'-thioadenosine, except that the intermediate 2',3'-epoxide 9 was first protected as the 5'-O-tert-butyldiphenylsilyl ether prior to subsequent synthetic steps. This hydrophobic silyl group facilitated extraction and isolation of synthetic intermediates. After removal of the protecting groups, the 3'-thionucleosides (C, G, U, and I) were treated with 2,2'-dipyridyl disulfide to protect the free thiol group as a disulfide. The 3'-thionucleosides were converted to the corresponding phosphorothioamidites using procedures analogous to those for standard Phosphoramidites. The amino groups of 3'-thiocytidine and 3'-thioguanosine were protected as benzoyl and isobutyryl amides, respectively, and the 5'- and 2'-hydroxyl groups of each nucleoside were protected as dimethoxytrityl and tert-butyldimethylsilyl ethers, respectively. The 3'-thiol group was deprotected by reduction with DTT and phosphitylated to afford analytically pure 3'-S-phosphorothioamidites 15, which were incorporated into oligoribonucleotides by solid-phase synthesis. Chemical assays and mass spectrometry of the synthetic RNA showed that ribose-3'-S-phosphorothiolate linkages were installed correctly and efficiently into RNA oligonucleotides using Phosphoramidite chemistry.
Qing Dai - One of the best experts on this subject based on the ideXlab platform.
-
preparation of dna containing 5 hydroxymethyl 2 deoxycytidine modification through Phosphoramidites with tbdms as 5 hydroxymethyl protecting group
Current protocols in human genetics, 2011Co-Authors: Qing DaiAbstract:This unit describes procedures for preparation of two Phosphoramidite building blocks III and IV, both containing a TBDMS as 5-CH2OH-protecting group. Phosphoramidites III and IV allow efficient incorporation of 5-hmC into DNA and a “one-step” deprotection procedure to cleanly remove all the protecting groups. A “two-step” deprotection strategy is compatible with ultramild DNA synthesis, which enables the synthesis of 5hmC-containing DNA with additional modifications. Methods are also presented for their incorporation into oligonucleotides by solid-phase synthesis, subsequent deprotection, and HPLC analysis. Curr. Protoc. Nucleic Acid Chem. 47:4.47.1-4.47.18. © 2011 by John Wiley & Sons, Inc. Keywords: 5-Hydroxymethylcytosine; DNA modification; oligodeoxyribonucleotide (ODN); Phosphoramidite; solid-phase synthesis; genomic DNA; epigenetic; ultramild deprotection
-
syntheses of 5 formyl and 5 carboxyl dc containing dna oligos as potential oxidation products of 5 hydroxymethylcytosine in dna
Organic Letters, 2011Co-Authors: Qing DaiAbstract:To investigate the potential oxidation products of 5-hydroxymethylcytosine (5-hmC)-containing DNA, we present here efficient syntheses of 5-formyl- and 5-methoxycarbonyl-2′-deoxycytidine Phosphoramidites. The 5-formyl group in III was easy to introduce and was compatible with Phosphoramidite and DNA syntheses. An additional treatment of ODN1 with NaBH4 produced the corresponding ODN2 quantitatively. Phosphoramidite V was also incorporated into DNA, and the methyl ester could be hydrolyzed under mild basic conditions to afford ODN3.
Ronald Micura - One of the best experts on this subject based on the ideXlab platform.
-
access to 3 deazaguanosine building blocks for rna solid phase synthesis involving hartwig buchwald c n cross coupling
Organic Letters, 2019Co-Authors: Elisabeth Mairhofer, Laurin Flemmich, Christoph Kreutz, Ronald MicuraAbstract:3-Deazaguanosine (c3G) and Phosphoramidite derivatives thereof that allow incorporation of this modification into RNA are needed for atomic mutagenesis experiments to explore mechanistic aspects of ribozyme catalysis. Here, we report a practical synthesis for c3G Phosphoramidites from inexpensive starting materials. The key reaction sequence is a silyl-Hilbert–Johnson nucleosidation followed by Hartwig–Buchwald cross-coupling to achieve the N2-phenoxyacetyl protected c3G nucleoside.
-
Access to 3‑Deazaguanosine Building Blocks for RNA Solid-Phase Synthesis Involving Hartwig–Buchwald C–N Cross-Coupling
2019Co-Authors: Elisabeth Mairhofer, Laurin Flemmich, Christoph Kreutz, Ronald MicuraAbstract:3-Deazaguanosine (c3G) and Phosphoramidite derivatives thereof that allow incorporation of this modification into RNA are needed for atomic mutagenesis experiments to explore mechanistic aspects of ribozyme catalysis. Here, we report a practical synthesis for c3G Phosphoramidites from inexpensive starting materials. The key reaction sequence is a silyl-Hilbert–Johnson nucleosidation followed by Hartwig–Buchwald cross-coupling to achieve the N2-phenoxyacetyl protected c3G nucleoside
Wolfgang Pfleiderer - One of the best experts on this subject based on the ideXlab platform.
-
nucleotides part xlvi the synthesis of phospholipid conjugates of antivirally active nucleosides by the improved Phosphoramidite methodology
Helvetica Chimica Acta, 1996Co-Authors: Harald Sigmund, Wolfgang PfleidererAbstract:The application of the improved Phosphoramidite strategy for the synthese of oligonucleotides using β-eliminating protecting groups to phospholipid chemistry offers the possibility to synthesize phospholipid conjugates of AZT (6) and cordycepin. The synthesis of 3′-azido-3′-deoxythymidine (6) was achieved by a new isolation procedure without chromatographic purification steps in an overall yield of 50%. Protected cordycepin ( = 3′-de-oxyadenosine) derivatives, the N6,2′-bis[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin (12) and the N6,5′-bis[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin (13) wre prepared by known methods and direct acylation of N6-[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin (9), respectively. These protected nucleosides and the 3′-azido-3′-de-oxythymidine (6) reacted with newly synthesized and properly characterized lipid-Phosphoramidites 21–25, catalyzed by 1H-tetrazole, to the corresponding nucleoside-phospholipid conjugates 26–38 in high yield. The deprotection was accomplished via β-elimination with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in aprotic solvents to give analytically pure nucleoside-phospholipid diesters 39–51 as triethylammonium or sodium salts. The newly synthesized compounds were characterized by elemental analyses and UV and 1H-NMR spectra.
-
nucleotides part xliii solid phase synthesis of oligoribonucleotides using the 2 dansylethoxycarbonyl 2 5 dimethylamino naphthalen 1 yl sulfonyl ethoxycarbonyl dnseoc group for 5 hydroxy protection
Helvetica Chimica Acta, 1994Co-Authors: Frank Bergmann, Wolfgang PfleidererAbstract:A new efficient method for solid-phase synthesis of oligoribonucleotides via the Phosphoramidite approach is described. The combination of the base-labile 2-dansylethoxycarbonyl (Dnseoc) group for 5′-OH protection with the acid-labile tetrahydro-4-methoxy-2H-pyran-4-yl (Thmp) group as 2′-OH blocking group is orthogonal regarding cleavage reactions and fulfills the requirements of an automated synthesis in an excellent manner if the Phosphoramidite function carries the N,N-diethyl-O-[2-(4-nitrophenyl)ethyl] substitution.
-
nucleotides part xli the 2 dansylethoxycarbonyl 2 5 dimethylamino naphthalen 1 yl sulfonyl ethoxycarbonyl dnseoc group for protection of the 5 hydroxy function in oligodeoxyribonucleotide synthesis
Helvetica Chimica Acta, 1994Co-Authors: Frank Bergmann, Wolfgang PfleidererAbstract:The 2-dansylethoxycarbonyl (Dnseoc) group was employed for protection of the 5′-hydroxy function in oligoribonucleotide synthesis by the Phosphoramidite approach using the acid-labile tetrahydro-4-methoxy-2H-pyran-4-yl (Thmp) group for 2′-protection. The syntheses of monomeric building blocks, both Phosphoramidites and nucleoside-functionalized supports, are described for the four common nucleosides adenosine, guanosine, cytidine, and uridine, and for the two modified minor nucleosides ribothymidine (= ribosylthymine) and pseudouridine.
Johannes G De Vries - One of the best experts on this subject based on the ideXlab platform.
-
enantioselective intramolecular reductive heck reaction with a palladium monodentate Phosphoramidite catalyst
Chemcatchem, 2017Co-Authors: Subramaniyan Mannathan, Johannes G De Vries, Joost N H Reek, Saeed Raoufmoghaddam, Adriaan J MinnaardAbstract:A palladium-catalyzed enantioselective reductive Heck reaction of enones using monodentate Phosphoramidite ligands is described. TADDOL-based Phosphoramidites with palladium(ll) acetate, and N-methyl dicyclohexylamine as reducing agent gives the reductive Heck product in high yields and enantioselectivities up to 90%. The solvent plays an important role and in diethyl carbonate the chemo and enantioselectivity appeared to be the highest.
-
a mixed ligand approach enables the asymmetric hydrogenation of an α isopropylcinnamic acid en route to the renin inhibitor aliskiren
Organic Process Research & Development, 2007Co-Authors: Jeroen A F Boogers, Ulfried Felfer, Martina Kotthaus, Laurent Lefort, Gerhard Steinbauer, And Andre H M De Vries, Johannes G De VriesAbstract:An asymmetric hydrogenation process for the α-isopropyl dihydrocinnamic acid derivative 2, an intermediate for the renin inhibitor aliskiren (4), has been developed using a rhodium catalyst ligated with a chiral monodentate Phosphoramidite and a nonchiral phosphine. Whereas catalysts based on two equivalents of monodentate Phosphoramidites gave promising results, the rate of hydrogenation and ee of the product could be improved spectacularly by the addition of monodentate nonchiral triarylphosphines to these catalysts. This remarkable mixed-ligand catalyst has been identified using high-throughput experimentation. With the best catalysts turnover numbers >5000 mol mol-1, turnover frequencies >1000 mol mol-1 h-1, and ee's up to 95% have been achieved.
-
rh catalyzed asymmetric hydrogenation of prochiral olefins with a dynamic library of chiral tropos phosphorus ligands
ChemInform, 2006Co-Authors: Chiara Monti, Johannes G De Vries, Cesare Gennari, Umberto Piarulli, Andre H M De Vries, Laurent LefortAbstract:A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 Phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium-catalyzed asymmetric hydrogenation of dehydro-α-amino acids, dehydro-β-amino acids, enamides and dimethyl itaconate. ee values up to 98% were obtained for the dehydro-α-amino acids, by using the best combination of ligands, a phosphite [4-P(O)2O] and a Phosphoramidite [13-P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4-P(O)2O] and Phosphoramidite [13-P(O)2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2-acetamidoacrylate and methyl 2-acetamidocinnamate faster than the mixture of the same phosphite with the Phosphoramidite, while the Phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/Phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv Phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/Phosphoramidite ratio is also presented.
