p-nitrobenzyloxymethyl: A new fluoride-removable protecting group for ribonucleoside 2′-hydroxyls

Gough, G.R.; Miller, Tod J.; Mantick, Nancy A.

doi:10.1016/0040-4039(95)02357-7

Cited by 35 publications

(24 citation statements)

References 12 publications

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“…While the TBDMS method gives RNA of reasonable purity in reasonable yield, both yield and purity are sensitive to small changes in the synthetic conditions. Furthermore, the TBDMS group is associated with relatively long coupling times (11) and insufficiently high coupling yields (12), though improvements based on the use of more powerful activators or less bulky 2′-hydroxyl protecting groups have been proposed (12). To resolve these pro-blems, three new protecting groups, bis(2-acetoxyethyl-oxy)methyl (ACE) (13), triisopropylsilyloxymethyl (TOM) (14), and more recently t -butyldithiomethyl (DTM) (15), have been developed.…”

Section: Introductionmentioning

confidence: 99%

Chemical synthesis of a very long oligoribonucleotide with 2-cyanoethoxymethyl (CEM) as the 2′-O-protecting group: structural identification and biological activity of a synthetic 110mer precursor-microRNA candidate

Shiba¹,

Masuda²,

Watanabe³

et al. 2007

Nucleic Acids Research

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A long RNA oligomer, a 110mer with the sequence of a precursor-microRNA candidate, has been chemically synthesized in a single synthesizer run by means of standard automated phosphoramidite chemistry. The synthetic method involved the use of 2-cyanoethoxymethyl (CEM), a 2′-hydroxyl protecting group recently developed in our laboratory. We improved the methodology, introducing better coupling and capping conditions. The overall isolated yield of highly pure 110mer was 5.5%. Such a yield on a 1-μmol scale corresponds to 1 mg of product and emphasizes the practicality of the CEM method for synthesizing oligomers of more than 100 nt in sufficient quantity for biological research. We confirmed the identity of the 110mer by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, as well as HPLC, electrophoretic methods, and RNase-digestion experiments. The 110mer also showed sense-selective specific gene-silencing activity. As far as we know, this is the longest chemically synthesized RNA oligomer reported to date. Furthermore, the identity of the 110mer was confirmed by both physicochemical and biological methods.

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Section: Introductionmentioning

confidence: 99%

Chemical synthesis of a very long oligoribonucleotide with 2-cyanoethoxymethyl (CEM) as the 2′-O-protecting group: structural identification and biological activity of a synthetic 110mer precursor-microRNA candidate

Shiba¹,

Masuda²,

Watanabe³

et al. 2007

Nucleic Acids Research

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“…2,a). We observed that nucleotide 2 (protected with a 2'-O-[(S)-npeom] group) reacted faster than the corresponding diastereoisomer (protected with a 2'-O-[(R)-npeom] group) 6 ). Under these optimized conditions, racemization of the N-nboc-protected l-phenylalanine was observed only to a very small extent 7 ).…”

mentioning

confidence: 80%

“…Earlier, we [5] and others [6] had found that some nitrobenzyl-alcohol derivatives are cleaved upon treatment with F À -ions. Therefore, we first investigated such compounds as potential fluoride-labile nucleobase-protecting groups.…”

mentioning

confidence: 99%

Novel Fluoride-Labile Nucleobase-Protecting Groups for the Synthesis of 3′(2′)-O-Aminoacylated RNA Sequences

Stutz

Höbartner

Pitsch

2000

HCA

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Dedicated to Prof. Albert Eschenmoser on the occasion of his 75th birthday With the aim to develop a general approach to a total synthesis of aminoacylated t-RNAs and analogues, we describe the synthesis of stabilized, aminoacylated RNA fragments, which, upon ligation, could lead to aminoacylated t-RNA structures. Novel RNA phosphoramidites with fluoride-labile 2'-O-[(triisopropylsilyl)-oxy]methyl ( tom) sugar-protecting and N-{{2-[(triisopropylsilyl)oxy]benzyl}oxy}carbonyl ( tboc) baseprotecting groups were prepared (Schemes 4 and 5), as well as a solid support containing an immobilized N 6 -tboc-protected adenosine with an orthogonal (photolabile) 2'-O-[(S)-1-(2-nitrophenyl)ethoxy]methyl ( (S)-npeom) group (Scheme 6). From these building blocks, a hexameric oligoribonucleotide was prepared by automated synthesis under standard conditions (Scheme 7). After the detachment from the solid support, the resulting fully protected sequence 34 was aminoacylated with l-phenylalanine derivatives carrying photolabile N-protecting groups (3 42 and 43; Scheme 9). Upon removal of the fluoride-labile sugar-and nucleobaseprotecting groups, the still stabilized, partially with the photolabile group protected precursors 44 and 45, respectively, of an aminoacylated RNA sequence were obtained (Scheme 9 and Fig. 3). Photolysis of 45 under mild conditions resulted in the efficient formation of the 3'(2')-O-aminoacylated RNA sequence 46 (Fig. 4).Additionally, we carried out model investigations concerning the stability of ester bonds of aminoacylated ribonucleotide derivatives under acidic conditions (Table) and established conditions for the purification and handling of 3'(2')-O-aminoacylated RNA sequences and their stabilized precursors.

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“…The 4-NBOM group has been introduced [79] as a 2'-O-protecting group of ribonucleosides, using 1-(4-nitrobenzyloxymethyl)pyridinium chloride (42, prepared from 4-N02C6H4CH20CH2CI [80] and pyridine); the 4-NBOM group is stable to acids and bases, and can be removed with F-ion (TBAF in THF, 24 h, rt). A synthesis of monomer 43 is shown in Scheme 29.…”

Section: -Nitrobenzyloxymethyl (4-nbom) Groupmentioning

confidence: 99%

Reactions at Oxygen Atoms

Tsuchiya¹

2001

Glycoscience: Chemistry and Chemical Biology I–III

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p-nitrobenzyloxymethyl: A new fluoride-removable protecting group for ribonucleoside 2′-hydroxyls

Cited by 35 publications

References 12 publications

Chemical synthesis of a very long oligoribonucleotide with 2-cyanoethoxymethyl (CEM) as the 2′-O-protecting group: structural identification and biological activity of a synthetic 110mer precursor-microRNA candidate

Chemical synthesis of a very long oligoribonucleotide with 2-cyanoethoxymethyl (CEM) as the 2′-O-protecting group: structural identification and biological activity of a synthetic 110mer precursor-microRNA candidate

Novel Fluoride-Labile Nucleobase-Protecting Groups for the Synthesis of 3′(2′)-O-Aminoacylated RNA Sequences

Reactions at Oxygen Atoms

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