A Novel Synthesis of Nucleoside Methylphosphonates

Engels, Joachim W.; Jäger, Alfred

doi:10.1002/anie.198209121

Cited by 21 publications

(7 citation statements)

References 5 publications

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“…Dinucleoside methylphosphonates were synthesized according to published procedures (16,17). They were purified and separated into the individual diastereomers by silica gel chromatography with EE/MeOH or CHCl3/MeOH gradients.…”

Section: Experimental Synthesis and Preassigumentmentioning

confidence: 99%

Diastereomeric dinucleoside-methylphosphonates: determination of configuration with the 2-D NMR ROESY technique

Löschner¹,

Engels²

1990

Nucl Acids Res

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The determination of configuration at phosphorus in diastereomeric dinucleoside-methylphosphonates having the -O-P(= O)(-CH3)-O- internucleotide linkage with the NOE derived ROESY NMR technique is described for ApT, TpT, ApA, TpA and CpG. For this purpose ROE's from the P-CH3 group to the protons in the nearest neighbourhood were measured. These ROE's are different within diastereomeric pairs of a dimer enabling us to deduce the individual configuration. The validity of the method is proven in comparison with dimers of known configuration (ApT, TpT). Together with a recently published diastereoselective synthesis method a more homogeneous picture between physical properties and the corresponding configuration is provided. There is an improvement in our knowledge about the stereochemistry of these substances which could not be deduced from the data known before.

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Section: Experimental Synthesis and Preassigumentmentioning

confidence: 99%

Diastereomeric dinucleoside-methylphosphonates: determination of configuration with the 2-D NMR ROESY technique

Löschner¹,

Engels²

1990

Nucl Acids Res

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“…Historically, Ts’o and coworkers first described the synthesis of dimers of 2′-deoxyribonucleosides with a mP linkage in 1979 [ 10 ]. For many years, access to methylphosphonates was limited to dimers or short oligomers of DNA or 2′-OCH 3 RNA only [ 3 , 4 , 11 ], although solution and solid-phase syntheses of mP containing nucleic acids were continuously improved by Engels et al [ 12 ], Agarwal et al [ 13 ], Lebedev et al [ 14 ], Heliński et al [ 15 ], Reynolds et al [ 4 ], and Schell et al [ 16 ]. With respect to RNA, it was soon recognized that the 2′-OH in direct neighborhood to a 3′- O -methylphosphonate group makes this linkage unstable; strand cleavage is observed as a result of nucleophilic attack of the 2′-OH, providing a 5′-RNA fragment with cyclic 2′, 3′- O -methylphosphonate and the corresponding 3′-RNA fragment with a free 5′-OH group.…”

Section: Introductionmentioning

confidence: 99%

Chemical synthesis of RNA with site-specific methylphosphonate modifications

Flür¹,

Micura²

2016

Methods

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Methylphosphonate(mP)-modified RNA serves as valuable probe to evaluate biomolecular interactions between the nucleic acid backbone and binding partners, such as proteins or small molecules. Here, we describe an efficient workflow for the synthesis of RNA with a single mP modification in diastereomerically pure form. While the automated assembly of mP-modified RNA is straightforward, its deprotection under basic conditions is challenging; a carefully optimized step-by-step procedure is provided. In addition, we demonstrate purification and separation strategies for the RP and SP-configurated RNA diastereomers using a combination of anion-exchange and reversed-phase HPLC, and comment on troubleshooting if their separation appears difficult. Furthermore, we demonstrate the stereochemical assignment of short RP and SP mP-modified RNA diastereomers based on 2D ROESY NMR spectroscopy and we report on the impact of the mP modification on thermal and thermodynamic stabilities of RNA-DNA hybrid and RNA-RNA duplexes.

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“…The possibility of the use of bifunctional P III phosphitylating agents other than methyldichlorophosphine 11,12 for a large scale synthesis of dinucleotides was appealing, since it is known that MePCl 2 is highly reactive and therefore not a selective reagent. This causes serious problems, particularly when large-scale protocols are evaluated.…”

Section: Resultsmentioning

confidence: 99%

2'-OMe-Uridin-3'-yl (3',5')-5'-O-(2'-OMe-Cytidine)-methanephosphonothioates - new building blocks for synthesis of chimeric oligonucleotides

Woźniak¹,

Majzner²,

Stec³

2004

Arkivoc

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A Novel Synthesis of Nucleoside Methylphosphonates

Abstract: The complete manuscript of this communication appears in: Angew. Chem. Suppl. 1982, 2010. DOI:10.1002/anie.198220100

Cited by 21 publications

References 5 publications

Diastereomeric dinucleoside-methylphosphonates: determination of configuration with the 2-D NMR ROESY technique

Diastereomeric dinucleoside-methylphosphonates: determination of configuration with the 2-D NMR ROESY technique

Chemical synthesis of RNA with site-specific methylphosphonate modifications

2'-OMe-Uridin-3'-yl (3',5')-5'-O-(2'-OMe-Cytidine)-methanephosphonothioates - new building blocks for synthesis of chimeric oligonucleotides

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