O-Phosphorylation

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

O Phosphorylation of the tertiary hydroxyl and diphosphorylation of the primary hydroxyl, followed by decarboxylation and simultaneous expulsion of phosphate, gives isopentenyl diphosphate, the precursor of terpenoids,... 

Phosphorylation of enolate ions by dialkyl or diaryl phosphorochlori-dates gives exclusive O-phosphorylation and it appears that the product geometry in acyclic systems is determined by the polarity of the solvent and... 

In a study of the attack of the ambident nucleophile ethanolamine on a series of phosphorylating agents (48) and related compounds it was observed that the proportion of O-phosphorylation increased as R and R varied in the series McaN, RO, R and as X varied in the series R2PO, CN, F, this last giving exclusive 0-phosphorylation. These results were... 

A. Mononucleotides.—A new journal has appeared in the past year consisting of abstracts of papers published in the nucleotide and nucleic acid fields. The use of nucleosides and nucleotides as potential therapeutic agents has been reviewed. Nucleotides which have been prepared recently using conventional methods of phosphorylation include those derived from 6-methylthiopurine ribonucleoside (la), 5-methylsulphonyluridine (lb), l-(jS-D-ribofuranosyl)-2-pyrimidone (Ic), 3-(jS-D-ribofuranosyl)-4-pyrimidone (Id), and various thionucleosides. - O-Phosphorylated 3 -amino-3 -deoxythymidine (2a) and 5 -amino-5 -deoxythymidine (2b)... 

Mosher RH, DJ Camp, K Yang, MP Brown, WV Shaw, LC Vining (1995) Inactivation of chloramphenicol by O-phosphorylation. J Biol Chem 270 27000-27006. 

Diphenylphosphoryl azide also gives good conversion of primary alkyl and secondary benzylic alcohols to azides in the presence of the strong organic base diazabicyc-loundecane (DBU). These reactions proceed by O-phosphorylation followed by Sw2 displacement.78... 

Other studies by Chen et al.35 have focused on how O-GlcNAcylation and O-phosphorylation can induce relevant differences in the structural and functional behaviour of the /V-terminus of Murine Estrigen Receptor b (mER-b). By using NOE data, chemical shift perturbations of NH protons and molecular dynamics simulations, subtle differences in the secondary structure of the characterized peptides were identified. 

The regiospecificity of the exclusive O-acylation [8] and O-phosphorylation [9] of P-dicarbonyl compounds (Chapter 3) also illustrates the effect of phase-transfer catalysts on the stereochemical course of reactions. Similarly, directed reduction of P-hydroxy ketones using tetramethylammonium trisacetoxyborohydride leads to the preferential formation of the anti dihydroxy system in high yield with a stereoselectivity >95% [10] (Section 11.4). 

The phosphine oxide adduct [Pr(dpm)3(OPPh3)] is of interest as although Pr3+ is a large ion, and Ph O is not perhaps too sterically demanding except at a distance from the ion, only a seven-coordinated mono adduct is obtained. The X-ray structure292 shows Pr—O(diketone) = 2.30-2.39 and Pr—O(phosphoryl) = 2.35 A. The comparatively short Pr-phosphoryl link is to be noted (compare Section 39.2.4.4) and would increase repulsion between the ligating atoms. The seven-coordination is in agreement with the solution studies mentioned above.283... 

Although the metaphosphate mechanism for hydrolysis is well documented, such a pathway remains to be demonstrated in a biological system. Our present knowledge of many enzymic reactions allows, at best, the formulation of a preliminary mechanism, i.e. the chemical identity of substrates and enzymic intermediates and the minimal kinetic scheme. For example, much recent attention has been focused on the remarkable stability of the covalent phos-phoryl-enzyme (an O-phosphoryl serine) derived from E. coii alkaline phosphatase28 and inorganic phosphate, and on a systematic kinetic study of the enzyme s substrate specificity (O-, N- and S-monoesters) -9. Dephosphorylation of the enzyme, however, does not appear to be via a metaphosphate mechanism30. 

Scheme I shows the hydrolysis of a phosphate ester in the presence of tris, which can serve as a phosphate acceptor so that O-phosphoryl-tris is a product as well as P(. It has been shown that in the presence of alcohols such as tris and ethanolamine the rate of substrate utilization is increased, that formation of alcohol exceeds that of phosphate, and that the difference is due to the formation of the O-phosphorylamino alcohol (122, 128). The question was Does the reaction with water and with tris emanate from the Michaelis complex or from a phosphoryl enzyme intermediate (E-P) If the reactions with tris and water stem from a phosphoryl enzyme, the ratio of products tris-phosphate and Pi would be independent of the leaving group RO, but if the reactions stem from the reversible complex containing the leaving group, the ratio of products would depend upon the structure of R. It was found that the ratio of free alcohol to phosphate was 2.39 0.02 for nine different substrates, including esters such as p-cresyl phosphate / -naphthyl phosphate, and phosphoenol pyruvate. This experiment established the occurrence of a phosphoryl enzyme intermediate.

Reaction of 4,5-disubstituted imidazole 1-oxides 263 with POCl3 or POBr3 produces 2-chloro or 2-bromoimidazole 301 (Hal = Cl or Br) (1975JCS(P1)275, 2002AG(E)2290). A possible mechanism in line with that in play by acylation comprises O-phosphorylation to be followed by addition of halogenide ion and subsequent elimination of halophosphoric acid as outlined in Scheme 89. 

Acylation, O-silylation, or O-phosphorylation, expected to follow the trends observed for 3-substituted imidazole 1-oxides, have not been reported. 

The same ligand types include o-phosphoryl phenols and di[alkyl(aryl)diphospho-nyl]methanes, for which the complexes of types 293 and 294 [552] are characteristic. In this respect, it is worth noting that, on the basis of alkyl(aryl)diphosphonyl-methanes, molecular chelates 294 [552] are formed instead of ICC. 

In reaction with amidophosphites hydroxymethylindole 80a gives the N-phosphorylation (80) and O-phosphorylation (81) products [77], At -5°C compound 80 is formed preferentially (80-85%) if the temperature is raised to 80°C its fraction amounts to 65-70%, while that of the O-phosphorylation product 81 is 30-35%. With a twofold excess of the amidophosphite instead of equimolar amount it is possible to obtain the diphosphorylated derivatives of 3-methylindole (82). All the compounds with a tricoordinated phosphorus atom (80-82) are easily oxidized in air to the corresponding compounds with a tetracoordinated phosphorus atom (83-85) ... 

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