Phosphorylation of phenols

Phenylphosphate synthase consists of three subunits with molecular masses of 70, 40, and 24kDa. Subunit 1 resembles the central part of classical phospho-enolpyruvate synthase which contains a conserved histidine residue. It catalyzes the exchange of free [ C] phenol and the phenol moiety of phenylphosphate but not the phosphorylation of phenol. Phosphorylation of phenol requires subunit 1, MgATP, and another protein, subunit 2 (40kDa), which resembles the N-terminal part of phosphoenolpyruvate synthase. Subunit 1 and 2 catalyze the following reaction ... 

Narmandakh A, N Gad on, F Drepper, B Knapp, W Haehnel, G Fuchs (2006) Phosphorylation of phenol by phenylphosphate synthase role of histidine phosphate in catalysis. J Bacteriol 188 7815-7822. 

Phosphorylation of phenolate anions with dimethyl phosphorochloridothionate in water-dichloromethane systems normally gives large amounts of dithiopyrophos-phate because of extensive hydrolysis of the phosphorus chloride, but in the presence of tetrabutylammonium salts and 1 % imidazole, phosphorylation of the phenolate anion is complete. The explanation lies in an evident combination of activation of acylating agent (by imidazole) and of nucleophile (by phase-transfer catalysis).71... 

General Procedure for the Phosphorylation of Phenol with Diethyl Chlorophosphonate on the Surface of Magnesia. Magnesia (0.3 g) was added to a mixture of diethyl chlorophosphonate (0.86 mL, 6 mmol) and the phenol (5 mmol). This mixture was stirred at room temperature or 60 °C for 0.25-1 h. The solid mixture was washed with dichloromethane (4x25 mL). The solution was then washed with a dilute NaOH solution and a saturated sodium chloride solution and dried over MgS04. After evaporating of solvent, the crude product was isolated in a pure state by distillation in vacuo in 85-95% yield. 

The phosphorylation of phenol-furfural condensate affords a cation-exchange resin with improved thermal and chemical reristance. The heat treatment of phosphonic add resins from furfural redns, phenol-resorcinol-formaldehyde resin, and polystyrene at 100-180 °C for 10-48 h shows that the furfural-based phosphonic acid resins possess higher thermal stability than those from the other two polymers. 

Synthesis of Phosphoric Acids and their Derivatives. - Among various approaches to phosphate esters the phosphorylation of phenols with dialkyl cyanophosphonate and the synthesis of triaryl phosphates under phase-transfer conditions are worthy of mention. Mixed trialkyl phosphates are also reported to be formed by brief cathodic electrolysis of the reaction of dialkyl phosphonates with aromatic aldehydes and ketones, presumably by rearrangement of the initial a-hydroxy compounds. Further reports have appeared of the generation of metaphosphates by various methods. The synthesis of analogues 1 of famesyl pyrophosphate which incorporate photoactive esters has been reported both compounds are competitive inhibitors of farnesyl transferase. 

Guzman. A., and Diaz, E., A convenient method for the phosphorylation of phenols with diethyl cyanophosphonate, Synth. Commun., 27, 3035, 1997. 

Phosphate esters are employed in febricated articles where flame retardancy is essential. These specialty plasticizers are made by phosphorylation of phenol or substituted phenols with POCl, (phosphorous oxychloride). The reaction for triphenyl phosphate is ... 

PTKs catalyze the phosphorylation of phenolic group of tyrosine residue in many substrate proteins by the transfer of c-phosphate moiety of ATP. PTKs play a crucial role in the signal transduction pathways. Aberrant regulation of kinase activity has been implicated in many diseases including cancer. 

The phosphoryl group in phenylphosphate is derived from the -phosphate group of ATP. The free energy of ATP hydrolysis obviously favors the trapping of phenol K, 0.04 mM), even at a low ambient substrate concentration. The reaction is stimulated several fold by another protein, subunit 3 (24kDa). The molecular and catalytic features of phenylphosphate synthase resemble those of phosphoenolpyruvate synthase, albeit with interesting modifications. ... 

Combined dipole moment and Kerr effect studies are regularly used by Russian workers for the conformational analysis of phosphorus heterocyc1es.135 230 In a study of the interaction of phenol with phosphoryl groups the Kerr effect was used to evaluate not only the extent of hydrogen bonding but also the influence of changes in polarity and polarisation upon stability constants.231 In a similar study the orientation of the aryl groups of 1,3,5-triazaphosphorines (82) were shown to be less coplanar than biphenyl in the gas phase. 2 3 2... 

Noting that the reaction of cycloheptaamylose with diphenyl pyrophosphate produces equal amounts of phenol, monophenyl phosphate, and phosphorylated cycloheptaamylose, Hennrich and Cramer (1965) proposed a nucleophilic mechanism (Scheme IV). According to this mechanism, a rapid, reversible association of the pyrophosphate with cycloheptaamylose... 

The catalysed two-phase adaptation of the Atherton-Todd procedure is effective for the phosphorylation of primary alcohols and of phenols [6] to produce trialkyl phosphates and dialkyl aryl phosphates. Trialkyl phosphates have also be obtained in high yield (>75%) from the alkylation of preformed tctra-n-butylammonium di-/-butylphosphate [7], Subsequent cleavage of the /-butyl groups provide a simple synthesis of monoalkyl phosphates. 

Atherton-Todd phosphorylation of alcohols and phenols (Table 3.22)... 

Diethyl phosphate esters of the sterically congested phenols of calixarenes have been prepared in acceptable yields (>55%) and used in the preparation of meta-cyclophanes [8]. The corresponding reaction using diethyl phosphite, with triethylamine in place of the quaternary ammonium catalyst, results in only partial phosphorylation of the hydroxyl groups. 

Table II. Uncoupling of Oxidative Phosphorylation by Phenols at pH 7.5 and Physicochemical Constants Used ...

The objectives of the studies reported herein were to (a) compare the effects of a series of phenolic acids, coumarins, and flavonoids on whole chain electron transport and phosphorylation in Isolated plant chloroplasts and mitochondria and (b) identify specific sites of inhibition with polarographic and enzymatic techniques. Exploratory studies were conducted with the 20 compounds listed in Table I. The three glycosides are shown indented below the corresponding aglycones. Detailed studies were conducted with the six compounds, one representative member from each chemical family, designated with an asterisk. 

Characteristics of toxicity for a number of metals are presented in Table 7.5. While the exact tissue and molecular site of the toxic action of each metal is different, toxicity generally results from interaction of the metal with specific functional groups on macromolecules in the cell. These groups include sulfhydryl, carboxyl, amino, phosphoryl, and phenolic moieties. Interactions of such groups with metals can lead to disruption of enzyme activities and transport processes and eventually... 

In disagreement with the above indications was the finding of Aldridge et al. (146) that for enzyme which was phosphorylated at pH 5.5 with inorganic phosphate and rapidly mixed with buffer at pH 8.4, the rate of dephosphorylation was twice as fast as the turnover of the enzyme at pH 8.0. Also, transient state kinetic studies by Femley and Walker (99, 110) showed a rapid release (burst) of phenol followed by a steady state release of phenol, only at pH < 7. Thus, these data would seem to indicate that at pH >7 the rate determining step is phosphorylation. 

Lower members of the series of salts formed between organic sulfoxides and perchloric acid are unstable and explosive when dry. That from dibenzyl sulfoxide explodes at 125°C [1], Dimethyl sulfoxide explodes on contact with 70% perchloric acid solution [2] one drop of acid added to 10 ml of sulfoxide at 20° C caused a violent explosion [3], and dibutyl sulfoxide behaves similarly [4]. A fatal explosion resulted from mistakenly connecting a DMSO reservoir to an autopipette previously used with perchloric acid [5], (The editor has met a procedure for methylthiolation of aromatics where DMSO was added to excess 70% perchloric acid he did not feel justified in trying to scale it up.) Explosions reported seem usually to result from addition to excess sulfoxide. Aryl sulfoxides condense uneventfully with phenols in 70% perchloric acid, but application of these conditions to the alkyl sulfoxide (without addition of the essential phosphoryl chloride) led to a violent explosion [4]. Subsequent investigation showed that mixtures of phenol and perchloric acid are thermally unstable (ester formation ) and may decompose violently, the temperature range depending on composition. DSC measurements showed that sulfoxides alone... 

However, two other areas are of interest (Fig. 9) namely, a) derivatisation of phenols or amines to phosphorus-containing compounds and b) on-column methylation. In the former, phosphorylation of 7 alcohols and 12 phenols with diethyl chlorophosphate in the presence of triethylamine at 60-70 C in benzene has been reported (35). Aliphatic alcohols, such as methanol, butanol or isoamyl alcohol react instantaneously while phenol and cresols require ca 1-1 1/2 hrs. and xylenols 3-4 hrs. for best results. 

Phosphorylation. Dibenzyl phosphorochloridate is widely used for phosphorylation of alcohols, but is more difficult to prepare than the fluoridate. Phenol is very readily phosphorylated by 1 and CsF in CH3CN, and indeed a phenolic hydroxyl group is selectively attacked even in the presence of a primary hydroxyl group. Primary and anomeric alcohols are preferentially phosphorylated in the presence of a secondary hydroxyl group. Alcohols that are insoluble in acetonitrile can be phosphorylated by 1 and DBU in place of CsF. 

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