Phosphorofluoridates phosphorylation

The mechanism by which A-esterases hydrolyze organophosphates is not completely understood. Involvement of a phosphorylated active-site cysteine and displacement of an activated H20 molecule are two possible hypotheses (see Sect. 3.7.1) [56], A-Esterases comprise enzymes that hydrolyze aryl esters, paraoxon (2.2) and related organophosphate pesticides, and diisopropyl-fluorophosphate (DFP, diisopropyl phosphorofluoridate, 2.3) and related compounds, including nerve gases. These enzymes are found in the current nomenclature listed under arylesterases, aryldialkylphosphatase, and diisop-ropyl-fluorophosphatase. 

Damodaran, T.V., Abdel-Rahman, A.A., Suliman, H.B., Ahou-Donia, M.B. (2002c). Early differential elevation and persistence of phosphorylated cAMP-response element binding protein (p-CREB) in the central nervous system of hens treated with diisopropyl phosphorofluoridate, an OPIDN-causing compound. Neurochem. Res. 27 183-93. 

Gupta, R.P., Ahou-Donia, M.B. (1999). Tau phosphorylation by diisopropyl-phosphorofluoridate (DFP)-treated hen brain supernatant inhibits its binding with microtubules role of Ca Vcalmodulin-dependent protein kinase II in tau phosphorylation. Arch. Biochem. Biophys. 365 268-78. 

Trimethylsilyl phosphorohalidates (6) and (7) have been synthesized from phosphoryl dihalogenofluoride (8) and hexamethyldisiloxane (9). An alternative approach to (7) using bis(trimethylsilyl) phosphorofluoridate (10) has been also elaborated (Scheme 1). Compounds (6) and (10) are involved in a new synthesis of bis(trimethylsilyl) diphosphorodifluoridate (11). ... 

In order to examine the stereochemical implications in the synthesis of (largely) phosphinic acids (but also tertiary phosphine oxides), Inch and coworkers " employed carbohydrate frameworks as chiral templates. As primary substrates, the cyclic phospho-rochloridate 161 and the corresponding phosphorofluoridate 162 were prepared from methyl 1,2,3-di-O-methyl-a-D-glucopyranoside, each phosphoryl halide being obtained as a mixture of diastereoisomers, anomeric at phosphorus, and from which, in each case, the major component (thought to have an equatorial P=0 bond) was isolated. Configurations in both substrates and reaction products were assigned with the aid of proton and NMR... 

The 3, 5 -cyclic phosphorofluoridate of thymidine has been prepared, whilst phosphorylation of AMP with cyclo-triphosphate gives a separable mixture of the 2, 5 - and 3, 5 -diphosphates. ... 

Phosphoryl halides are obtained from phosphorus pentahalides (4.53) or hydrogen halides (4.54), but with hydrogen fluoride, the product is hexafluorophosphoric acid (4.293) or phosphorofluoridic acid (5.264). 

Phosphorofluoridic acid (monofluorophosphoric acid) and phosphorodifluoridic acid (difluorophos-phoric acid) are produced in the intermediate stages of hydrolysis of phosphoryl fluoride, and can be isolated under suitable conditions. 

A new phosphorylating reagent, dibenzyl phosphorofluoridate, has been introduced. In the presence of caesium fluoride as base it reacts with primary and anomeric hydroxy groups preferentially. Secondary hydroxy groups, e.q.. those of partially protected myo-inositol, can be phosphorylated after deprotection with butyl lithium. 1,2-Di-phosphates were obtained in good to excellent yields by treatment of vicinal diols with diethyl phosphorochloridate and butyl lithium there was no evidence of formation of cyclic phosphates, the predominant products when other bases are used. Q-Glycosylation of phosphonic and phosphinic acids has been achieved by the trichloroacetimidate method examples are given in Scheme 4. ... 

A. R. Main and F. Iverson, Measurement of the affinity and phosphorylation constants governing irreversible inhibition of cholinesterases by diisopropyl phosphorofluoridate, Biochem. J., 1966, 100, 525-531. 

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