Phosphate esters cyclic

Biological chemistry of phosphate esters cyclic substrates and transition states. 212... 

In the example shown the 5 OH group is phosphorylated Nucleotides are also possible in which some other OH group bears the phosphate ester function Cyclic phosphates are common and important as biochemical messengers... 

In the example shown, the 5 -OH group is phosphorylated. Nucleotides ae also possible in which sorme other OH group beas the phosphate ester-function. Cyclic phosphates ae cormrmon and irmportant as biochermical rmessengers. 

DNA is not susceptible to alkaline hydrolysis. On the other hand, RNA is alkali labile and is readily hydrolyzed by dilute sodium hydroxide. Cleavage is random in RNA, and the ultimate products are a mixture of nucleoside 2 - and 3 -monophosphates. These products provide a clue to the reaction mechanism (Figure 11.29). Abstraction of the 2 -OH hydrogen by hydroxyl anion leaves a 2 -0 that carries out a nucleophilic attack on the phosphorus atom of the phosphate moiety, resulting in cleavage of the 5 -phosphodiester bond and formation of a cyclic 2, 3 -phosphate. This cyclic 2, 3 -phosphodiester is unstable and decomposes randomly to either a 2 - or 3 -phosphate ester. DNA has no 2 -OH therefore DNA is alkali stable. 

B. Solvolysis of Phosphoric Acid Derivatives.—Interest continues in neighbouring-group participation in the solvolysis of phosphate esters. As a potential model compound for investigating the mechanism of ribo-nuclease action, the phenyl hydrogen phosphate ester of c/j-3,4-tetrahydro-furandiol (24) has been the subject of a detailed study. Above (and probably also below) pH 4 hydrolysis gives solely the cyclic phosphate (25)... 

A. Phosphoenolpyruvate.—The mechanisms of hydrolysis of phosphate esters of phosphoenol pyruvic acid (33) have been described in detail, and 0 studies confirm an earlier postulate that attack by water on the cyclic acyl phosphate (34) occurs at phosphorus and not at carbon. In the enolase reaction, the reversible interconversion of 2-phosphoglyceric acid(35)... 

The factors involved and mechanistic pathways in the hydrolysis of phosphate esters, particularly those of a cyclic nature, continue to be the source of much speculation. A further study of the simplest cyclic triester, ethylene methyl phosphate, seems only to have served to consolidate already polarized views. The original, experiments of Westheimer s group employed gc and H nmr spectroscopy and demonstrated that ethylene methyl phosphate (26) hydrolyses under alkaline conditions by... 

Scheme 12 1,2-phosphatoxy shifts in a cyclic phosphate ester... 

Reactions of Phosphoric Acid and its Derivatives.—Theoretical studies on the conformational properties of cyclic and acyclic phosphate esters, including calculations of angle and torsional strain,66 and on the reactivity of monomeric metaphosphates,67 have appeared. 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

The fifth sapphyrin-phosphate structure to be solved is of the mixed chlo-ride/monobasic cyclic AMP salt of diprotonated sapphyrin 4 (Figure 9). While the general features of binding are similar to the other phosphate ester structures... 

The cyclic phosphonate may be intercepted with hydroxylamine to yield the corresponding hydroxamate. Importantly, the rate of hydroxylaminolysis is approximately the same as ethanol loss, thus it appears that the cyclic phosphonate and not a precursor pentacovalent species is being trapped. Insofar as the analogy is appropriate, hydroxylamine is trapping an acyclic acyl phosphate in the above case, albeit at a rate faster than benzyl alcohol loss. It is also noteworthy that for both the phosphonate and phosphate esters there is no net transfer of oxygen from the carboxyl to phosphorus during the entire course of hydrolysis, i.e. loss of two moles of alcohol. 

In the author s own laboratory the Cu(II)-catalyzed hydrolysis of the phosphate ester derived from 2-[4(5)-imidazolyl] phenol recently has been investigated146. The pertinent results are (a) the pre-equilibrium formation of a hydrolytically labile Cu(II)-substrate complex (1 1), (b) the occurrence of catalysis with the free-base form of the imidazolyl and phosphate moieties and (c) the extraordinary rate acceleration at pH 6 (104) relative to the uncatalyzed hydrolysis146. The latter recalls the unusual rate enhancement encountered above with five-membered cyclic phosphates and suggests a mechanism in which the metal ion, at the center of a square planar complex or a distorted tetrahedral complex, might induce strain in the P-O ester bonds (60). viz. 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

Ribonuclease T2 is regarded as a nonspecific endoribonuclease [EC 2.7.7.17, ribonucleate nucleotido-2 -transferase (cyclizing)]. It preferentially splits the internucleotide bonds between the 3 -adenylic acid group and the 5 -hydroxyl group of adjacent nucleotides in RNA, with the intermediary formation of adenosine 2, 3 -cyclic phosphate and splits consequently all secondary phosphate ester bonds of other nucleotides in RNA via the nucleotides 2, 3 -cyclic phopshates. 

Relative Rates of Hydrolysis of Various Phosphate Esters by Nucleoside 2, 3 -Cyclic Phosphate Diesterase... 

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