96730-04-0Relevant articles and documents
Nucleophilic 18F-fluorination of phosphorofluoridates and phosphonofluoridic acids via imidazole-activated precursors
Mou, Zhaobiao,Chen, Xueyuan,Wang, Chao,Wang, Tao,Yang, Hongzhang,Li, Zijing
, (2021/03/03)
18F-Labeled organofluorophosphates are important radiosynthons that have only been previously accessible via 18/19F-isotope-exchange with limited molar activities. Herein, a novel 18F-fluorination methodology has been developed to prepare 18F-labeled phosphorofluoridates and phosphonofluoridic acids via the [18F]F? nucleophilic substitution of imidazole-activated precursors. The efficient one-step 18F-fluorination affords stable products in the presence of Zn(Ⅱ) with high radiochemical yields and high molar activities. This 18F-fluorination method could be used to prepare various phosphorofluoridate and phosphonofluoridic acid analogs for use as 18F-radiosynthons and potential positron emission tomography tracers.
A Phosphoramidite Analogue of Cyclotriphosphate Enables Iterative Polyphosphorylations
Singh, Jyoti,Steck, Nicole,De, Debaditya,Hofer, Alexandre,Ripp, Alexander,Captain, Ilya,Keller, Manfred,Wender, Paul A.,Bhandari, Rashna,Jessen, Henning J.
supporting information, p. 3928 - 3933 (2019/02/20)
An iterative polyphosphorylation approach is described, which is based on a phosphoramidite (P-amidite) derived reagent (c-PyPA) obtained from the cyclization of pyrophosphate with a reactive diisopropylaminodichlorophosphine. This type of reagent is unprecedented as it represents a reactive P-amidite without protecting groups. The reagent proved to be stable in solution over several weeks. Its utility is described in the context of iterative monodirectional and bidirectional polyphosphorylations. The ensuing functionalized cyclotriphosphate can be opened with a variety of nucleophiles providing ready access to diverse functionalized polyphosphate chains of defined length with several tags, including both P-N and P-O labels. Their interaction with exo- and endopolyphosphatases is described.
Facile synthesis of simple mono-alkyl phosphates from phosphoric acid and alcohols
Dueymes, Cyril,Pirat, Céline,Pascal, Robert
, p. 5300 - 5301 (2008/12/22)
Simple aliphatic alcohols can be selectively converted into mono-alkyl phosphate esters at the laboratory scale using the acetic anhydride-mediated activation of inorganic phosphate.
Bis(carbamoyloxymethyl) esters of 2′,3′-dideoxyuridine 5′-monophosphate (ddUMP) as potential ddUMP prodrugs
Khan, Saeed R.,Kumar, Srinivas K.,Farquhar, David
, p. 390 - 396 (2007/10/03)
Purpose. We previously reported the synthesis of bis(pivaloyloxymethyl) 2′,3′-dideoxyuridine 5′-monophosphate (POM2-ddUMP) (1a) as a membrane-transport prodrug formulation of the free parent nucleotide, ddUMP. Although successful at delivering ddUMP into cells in culture, POM 2-ddUMP was rapidly degraded by plasma carboxylate esterases after intravenous administration to experimental animals, and therefore has limited therapeutic potential as a systemically administered prodrug. We now report the synthesis of bis(N,N′-dimethylcarbamoyloxymethyl)- and bis(N-piperidinocarbamoyloxymethyl) 2′,3′-dideoxyuridine 5′-m onophosphate [DM2-ddUMP (1b) and DP2-ddUMP (1c), respectively], analogues of POM2-ddUMP that were designed to be more resistant to degradation by plasma esterases. Methods. After entering cell by passive diffusion, it was anticipated that loss of one of the carbamoyloxymethyl groups of 1b and 1c would occur by spontaneous chemical hydrolysis to give the intermediate phosphodiesters, 2b and 2c. Cleavage of the remaining carbamoyloxymethyl groups by cellular phosphodiesterase I would generate ddUMP. 1b and 1c were prepared by condensation of 2′,3′-dideoxyuridine (ddU) with the appropriate bis(N-alkylcarbamoyloxymethyl) phosphate in DMA in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). Results. The half-lives of 1b and 1c when incubated at a concentration of 10-4 M in human plasma at 37°C were 3.5 h and 3.7 h, respectively, similar to the half-lives observed under the same temperature conditions in 0.05 M aqueous phosphate buffer, pH 7.4. By contrast, the half-life of the POM2 prodrug, 1a, in plasma was only 5 min. The initial products of degradation of 1b and 1c were the phosphodiesters 2b and 2c. The latter compounds gave rise to ddUMP when incubated with snake venom phosphodiesterase I. Conclusion. These findings support the premise inherent in the design of 1b and 1c, namely that the carbamate prodrugs are far more resistant to hydrolysis by plasma carboxylate esterases than their POM counterparts and can revert to the free parent 5′-mononucletides by successive chemical and enzymatic hydrolysis. Further studies of 1b and 1c as membrane-permeable prodrugs of ddUMP are in progress.
18O Isotope Effect in 13C Nuclear Magnetic Resonance Spectroscopy. 9. Hydrolysis of Benzyl Phosphate by Phosphatase Enzymes and in Acidic Aqueous Solutions
Parente, Jean E.,Risley, John M.,Etten, Robert L. Van
, p. 8156 - 8161 (2007/10/02)
The 18O isotope-induced shifts in 13C and 31P nuclear magnetic resonance (NMR) spectroscopy were used to establish the position of bond cleavage in the phosphatase-catalyzed and acid-catalyzed hydrolysis reactions of benzyl phosphate.The application of th
