Preparation, stability and acidity of difluoromethylene bis phosphonic acid

Burton, Donald J.; Pietrzyk, Donald J.; Ishihara, Takashi; Fonong, Tekum; Flynn, Richard M.

doi:10.1016/s0022-1139(00)82287-3

Cited by 29 publications

(19 citation statements)

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“…After 10 min, the reaction was complete ( 31 P NMR, δ −11.54 ppm (in CD 3 CN)). The product, dAMP- N -methylimidazolide , 42 was used for coupling reaction. In a separate flask, a solution of (1-phosphonoethyl)phosphonic acid derivative 40a or 40b (∼6–7 mg, either isomer) in 2 mL of EtOH/H 2 O (1:1) was adjusted to pH 8 by adding (Bu) 4 NOH (40% in water) and stirred for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations

et al. 2020

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Nucleoside 5′-triphosphate (dNTP) analogues in which the β,γ-oxygen is mimicked by a CXY group (β,γ-CXY-dNTPs) have provided information about DNA polymerase catalysis and fidelity. Definition of CXY stereochemistry is important to elucidate precise binding modes. We previously reported the (R)- and (S)-β,γ-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorpholinamide CHCl (6a, 6b) and CHF (7a, 7b) bisphosphonates (BPs) equipped with an (R)-mandelic acid as a chiral auxiliary, with final deprotection using H2/Pd. This method also affords the β,γ-CHCl-dTTP (11a, 11b), β,γ-CHF (12a, 12b), and β,γ-CHCl (13a, 13b) dATP diastereomers as documented here, but the reductive deprotection step is not compatible with dCTP or the bromo substituent in β,γ-CHBr-dNTP analogues. To complete assembly of the toolkit, we describe an alternative synthetic strategy featuring ethylbenzylamine or phenylglycine-derived chiral BP synthons incorporating a photolabile protecting group. After acid-catalyzed removal of the (R)-(+)-α-ethylbenzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual diastereomers of β,γ-CHBr- (33a, 33b), β,γ-CHCl- (34a, 34b), β,γ-CHF-dCTP (35a, 35b) were obtained. The β,γ-CH(CH3)-dATPs (44a, 44b) were obtained using a methyl (R)-(−)-phenylglycinate auxiliary. 31P and 19F NMR Δδ values are correlated with CXY stereochemistry and pK a2–4 values for 13 CXY-bisphosphonic acids and imidodiphosphonic acid are tabulated.

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Section: Methodsmentioning

confidence: 99%

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations

et al. 2020

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“…Reagents. The procedure for the synthesis and characterization of F2MDP is provided elsewhere (17). EHDP and C12MDP were obtained as disodium salts from the Department of Dentistry, University of Iowa.…”

Section: Methodsmentioning

confidence: 99%

“…EHDP and C12MDP were obtained as disodium salts from the Department of Dentistry, University of Iowa. Procedures for their purification and conversion to the free acid were similar to that used for F2MDP (17). All other salts used in the study were analytical reagent grade whenever possible.…”

Section: Methodsmentioning

confidence: 99%

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Determination of formation constants of calcium complexes of difluoromethylenediphosphonic acid and related diphosphonates

Fonong¹,

Burton²,

Pietrzyk³

1983

Anal. Chem.

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“…Diethyl difluoromethylphosphonate was also obtained by hydrolysis of tetraethyl difluoromethylenebisphosphonate with sodium hydroxide. 100 Oxidation reaction : The reaction of chiral ethylmethyl methylphosphonate with successively a strong base (n-BuLi) and perchloryl fluoride in THF yields a mixture of the corresponding difluoro and monofluorophosphonate. 33 An analogous process was applied to tetraethyl and tetraisopropyl methylenebisphosphonate with potassium tert-butoxide as a base in toluene.…”

Section: R T Omentioning

confidence: 99%

The Synthesis of Dialkyl α-Halogenated Methylphosphonates

Waschbüsch¹,

Carran²,

Marinetti³

et al. 1997

Synthesis

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Preparation, stability and acidity of difluoromethylene bis phosphonic acid

Cited by 29 publications

References 4 publications

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations

Determination of formation constants of calcium complexes of difluoromethylenediphosphonic acid and related diphosphonates

The Synthesis of Dialkyl α-Halogenated Methylphosphonates

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Preparation, stability and acidity of difluoromethylene bis phosphonic acid

Cited by 29 publications

References 4 publications

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and 31P and 19F NMR Correlations with Absolute Configurations

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and 31P and 19F NMR Correlations with Absolute Configurations

Determination of formation constants of calcium complexes of difluoromethylenediphosphonic acid and related diphosphonates

The Synthesis of Dialkyl α-Halogenated Methylphosphonates

Contact Info

Product

Resources

About

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and ³¹P and ¹⁹F NMR Correlations with Absolute Configurations