Aqueous methods for the preparation of 5′-substituted guanosine derivatives

Brear, P.; Freeman, Gemma R.; Shankey, Mark C.; Trmčić, Milena; Hodgson, David R. W.

doi:10.1039/b908727c

Cited by 20 publications

(26 citation statements)

References 15 publications

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“…Despite this process, we proceeded with Salkylation using MeI. This led to a majority of the P-containing product mixture being converted to S-methylated inorganic 25 phosphate ion 10. The large proportion of N-P bond scission suggests that once alkylated, intramolecular reaction facilitates this cleavage, unlike simple N,S-dialkyl thiophosphoramidates, which appear to be stable under the reaction conditions.…”

Section: Glucosaminementioning

confidence: 99%

“…20 To prove the general applicability of the method, we preparaed a small generic library of N,S-dialkyl thiophosphoramidates 20-33a-c in a simple, rapid manner where the only form of purification was extraction of excess alkylating agent followed by removal of the aqueous solvent. All amines were hydrophobic in 25 nature, and some of the reaction mixtures were heterogeneous. Alkylating agents were represented by benzyl chloride, n-propyl iodide and a quinoline system.…”

Section: Nucleophilicity Of Thiophosphoryl Systemsmentioning

confidence: 99%

“…Sulfur-based analogues have been used in place of phosphodiesters to both increase and decrease the rate of ester bond cleavage. Accelerated cleavage rates are offered by S-bridging systems, 1 where the thiolate leaving group departs more readily than its alkoxide analogue, whereas reduced 25 cleavage rates are seen for non-S-bridging systems. 2 Nitrogenbridging phosphodiester mimics, where N-protonation becomes possible, have also been generated and studied.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, phosphonamide systems have been widely exploited as transition state mimics for the attack of water upon the cabonyl of amides (Figure 1). To date, a limited number of examples of aqueous amino acid 25 phosphorylations have been reported. Metatriphosphate ion possesses an activated anhydride structure that has been shown to be an effective N-phosphorylating agent for amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…We envisioned 15 being able to react selectively with thiophosphoramidate ions to produce activate acylating agents 16 25 that could be further reacted with readily accesible amines to produce mixed phosphoryl-acyl systems 17 that may serve as pyrophosphate mimics (Scheme 8). Our earlier experiences with a thiophosphate anion-based system (uridine-5'-monophosphorothioate, UMPS), suggested that this strategy Based on our earlier work with thiophosphates, we performed exploratory studies on the use of p-nitrophenyl-, m-nitrophenyl and phenyl-bromoacetate esters 15a-c respectively.…”

mentioning

confidence: 99%

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Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing

Trmčić¹,

Chadbourne²,

Brear³

et al. 2013

Org. Biomol. Chem.

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(2013) 'Aqueous synthesis of N,S,-dialkylthiophosphoramidates : design, optimisation and application to library construction and antileishmanial testing. ', Organic and biomolecular chemistry., 11 (16). pp. 2660-2675. Further information on publisher's website:Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. We recently reported the use of PSCl 3 for the thiophosphorylation of alkylamines where the resulting Nthiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156-6158.). Herein 10 we report the development of this methodology using amino acid, amino sugar, aminonucleoside and aniline substrates. The hydrolysis properties of N-thiophosphoramidate ions and their reactivities towards alkylating agents are also explored. In addition, we demonstrate the application of our approach to the preparation of a small library of compounds, including quinoline-based N,S-dialkylthiophosphoramidates which were tested for antileishmanial activity.15

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Section: Glucosaminementioning

confidence: 99%

Section: Nucleophilicity Of Thiophosphoryl Systemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing

Trmčić¹,

Chadbourne²,

Brear³

et al. 2013

Org. Biomol. Chem.

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An RNase P‐Based Assay for Accurate Determination of the 5′‐Deoxy‐5′‐azidoguanosine‐Modified Fraction of in Vitro‐Transcribed RNAs

et al. 2018

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Chemoenzymatic approaches are important for generating site-specific, chemically modified RNAs, a cornerstone for RNA structure-function correlation studies. T7 RNA polymerase (T7RNAP)-mediated in vitro transcription (IVT) of a DNA template containing the G-initiating class III Φ6.5 promoter is typically used to generate 5'-chemically modified RNAs by including a guanosine analogue (G analogue) initiator in the IVT. However, the yield of 5'-G analogue-initiated RNA is often poor and variable due to the high ratios of G analogue:GTP used in IVT. We recently reported that a T7RNAP P266L mutant afforded an approximately three-fold increase in fluorescent 5'-thienoguanosine-initiated pre-tRNA compared to the wild type T7RNAP. We have further explored the use of T7RNAP P266L to generate 5'-deoxy-5'-azidoguanosine ( G)-initiated RNA and found that the mutant yielded approximately four times more G-initiated pre-tRNA than the wild type in an IVT containing a 10:1 ratio of G:GTP. For accurate quantitation of the 5'- G-initiated RNA fraction, we employed RNase P, an endonuclease that catalyzes the removal of the 5'-leader in pre-tRNAs. Importantly, we show herein how RNase P can be leveraged for assessing 5'-G analogue incorporation in any RNA by rendering the target RNA, upon its binding to a customized external guide sequence RNA, into an unnatural substrate of RNase P. Such an approach in conjunction with T7RNAP P266L-based IVT should aid chemoenzymatic methods that are designed to generate 5'-chemically modified RNAs.

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ChemInform Abstract: Aqueous Methods for the Preparation of 5′‐Substituted Guanosine Derivatives.

et al. 2009

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Aqueous methods for the preparation of 5′-substituted guanosine derivatives

Abstract: We have developed simple, aqueous strategies, that avoid the use of protecting groups and chromatography, for the preparation of a series of 5'-substituted guanosine derivatives.

Cited by 20 publications

References 15 publications

Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing

Aqueous synthesis of N,S-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing

An RNase P‐Based Assay for Accurate Determination of the 5′‐Deoxy‐5′‐azidoguanosine‐Modified Fraction of in Vitro‐Transcribed RNAs

ChemInform Abstract: Aqueous Methods for the Preparation of 5′‐Substituted Guanosine Derivatives.

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