Migration phosphoryl groups

Pyruvate kinase catalyzes the conversion of phospho-enolpyruvate and ADP to pyruvate and ATP. A proton is taken up in the reaction. The enzyme binds one K+ and two Mg + ions. The 2.9 A crystal structme shows that the K+ interacts directly with the migrating phosphoryl group and indirectly with residues in the active site. Activity with Na+ is about 9% that of K+. Figme 1 shows the geometry of the active site. Oxalyl phosphate is a substrate for pyruvate... 

The reaction course is determined by the heteroatom X. Since the migration of the silatranyl group to the oxygen of the phosphoryl group in the episulfonium intermediate is more preferable than that to sulfur, the a/b ratio is 3 2 and 6 1 for X = O and S, respectively. Similar sequences are likely to be involved in the reaction with 1 -allylsilatranes346. 

Not only alky] groups, but also aryl [492, 493], vinyl [494], acyl [276, 495—497], alkoxycarbonyl [498], aminocarbonyl [499-501], silyl [502-504], or phosphoryl groups [279, 280] can migrate to a vicinal carbanion (Scheme 5.68). Because some of these groups can be used to stabilize a-heteroatom-substituted carbanions by chelate formation, migration of these groups to the carbanion is a potential side reaction in the generation and alkylation of chelate-stabilized carbanions. 

In some cases, diethyl 1,2-epoxyalkylphosphonates undergo thermal phosphoryl group migration at high temperatures (170-300°C) to produce 1-substituted l-formylmethylphosphonates. However, this method has only limited utility because the rearrangement products themselves can be thermally labile with respect to dephosphorylation. >37,143,144... 

The formal migration of a phosphoryl group between the C6 and the Ci of glucose is catalyzed by phosphoglucomutase. Mechanistic studies were performed with the... 

A very clever three-phase test for the detection of metaphosphate intermediates in phosphoryl transfer reactions has been described by Rebek and coworkers (44). The basis of this test is the use of two polymers suspended in solution. The donor polymer contains a potential precursor to metaphosphate anion, e.g., an acyl phosphate or a phosphoramidate, and the recipient polymer contains an acceptor nucleophile, e.g., an amine. After reaction and physical separation of the polymers, the recipient polymer is analyzed for covalently bound phosphate. Since very few of the phosphoryl groups to be transferred will be on the surface of the donor polymer, detection of significant transfer to the recipient polymer provides evidence for a diffusible intermediate, i.e., free metaphosphate anion. Significant transfer did occur in dioxane or acetonitrile suspensions of the polymers, thereby providing evidence for an intermediate. However, this test for diffusible and, therefore, relatively stable metaphosphate anion is compromised by the choice of solvent. Both dioxane and acetonitrile can provide unshared electron pairs for the highly electrophilic metaphosphate anion such that the actual species that migrates from the donor polymer to the recipient polymer may be a complex between metaphosphate anion and the solvent. Such a role for solvent has been investigated stereochemically, the results of which will be described later in this section. 

The pH dependent chemical hydrolyses of the phosphorothioate analogues 2 -, 3 - and 5 -UMPS have been investigated. Between pH 2 and 5 dethio-phosphorylation is between 200 and 300 times faster than dephosphorylation due to the higher stability of the intermediate thiometaphosphate compared to the metaphosphate anion. At pH values less than 1, no migration of the thio-phosphoryl group takes place but rather, desulfurisation occurs. 

In another study, only the formation of tetraalkyl enolphosphonate phosphate was observed. The mechanism of its formation was elucidated (equation 15)". It was concluded that the initial product, an acylpseudophosphonium salt, added rapidly a second molecule of phosphite to form an ionic species which gave the final product after a carbon to oxygen migration of one of the phosphoryl groups, and the loss of two molecules of ethyl chloride. 

A different kind of reaction is observed in case of the photochemical and thermal reaction of an a-diazo-j -methoxy carbonyl acylphosphonate. The carbene formed after the loss of nitrogen rearranges to a ketene, by exclusive migration of the phosphoryl group (equation 83). ... 

In addition. Hall and Inch (1980b) have demonstrated that the overall stereochemistry of nucleophilic substitution may be complicated by secondary processes. Recyclization mechanisms (p. 158) readily compete with direet exoeyclie displacement, and may also result in phosphoryl group migration subsequent to initial ring eleavage (Harrison and Inch, 1979). Confusion due to competing pathways hinders rationalization of the observed overall stereochemistry and product distribution of nucleophilic substitution. 

This step removes the 5 phosphoryl group of excess ddNTPs that would otherwise co-migrate with the SNP fragment of interest. 

Migration of the phosphoryl group is liable to occur in such situations as [18]... 

Kinases not only bind ATP and other phosphoryl donors but also enhance the electrophilic-ity of the migrating phosphate group by coordination with one or two Mg " " ions. The mechanism of phosphoryl transfer is essentially an 8 2 reaction, which we may represent as shown below (B is an active site base). For clarity, we have not included any of the Mg " " ions in our simplified picture ... 

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