Pyrophosphate esters

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate are structurally sim liar—both contain a double bond and a pyrophosphate ester unit—but the chemical reactivity expressed by each is different The principal site of reaction m dimethylallyl pyrophosphate is the carbon that bears the pyrophosphate group Pyrophosphate is a reasonably good leaving group m nucleophilic substitution reactions especially when as in dimethylallyl pyrophosphate it is located at an allylic carbon Isopentenyl pyrophosphate on the other hand does not have its leaving group attached to an allylic carbon and is far less reactive than dimethylallyl pyrophosphate toward nucleophilic reagents The principal site of reaction m isopentenyl pyrophosphate is the carbon-carbon double bond which like the double bonds of simple alkenes is reactive toward electrophiles... 

The product of this reaction is geranyl pyrophosphate Hydrolysis of the pyrophosphate ester group gives geramol a naturally occurring monoterpene found m rose oil... 

Hydrolysis of the pyrophosphate ester group converts farnesyl pyrophosphate to the corresponding alcohol farnesol (see Figure 26 6 for the structure of farnesol)... 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

C. Reactions.—The iV-chloroquinonimine (50) reacts with monoalkyl phosphates in dry pyridine to give symmetrical pyrophosphate esters. If present in excess it can react further, giving an intermediate which is attacked by alcohols or water with cleavage of the pyrophosphate bond. 

Acid dye method for the analysis of thiamin, 18A, 73 electrophoretic separation and fluorometric determination of thiamin and its phosphate esters, 18A, 91 catalytic polarography in the study of the reactions of thiamin and thiamin derivatives, 18A, 93 preparation of thiamin derivatives and analogs, 18A, 141 preparation of the mono- and pyrophosphate esters of 2-methyl-4-amino-5-hydroxymethylpyrimidine for thiamin biosynthesis, 18A, 162 formation of the pyrophosphate ester of 2-methyl-4-amino-5-hydroxymethylpyrimidine by enzymes from brewers yeast in thiamin biosynthesis, 18A, 203 resolution, reconstitution, and other methods for the study of binding of thiamin pyrophos-... 

Vitamin deficiency of Bj leads to the disease known as Beriberi. However, nowadays in the Western hemisphere, vitamin Bj deficiency is mainly found as a consequence of extreme alcoholism. In fact, the vitamin absorption by the gut is decreased and its excretion is increased by alcohol. Alcohol also inhibits the activation of vitamin Bj to its coenzyme form, thiamine pyrophosphate ester (TPP). There is no evidence of adverse effects of oral intake of thiamine [417]. The main food sources of vitamin Bj are lean pork, legumes, and cereal grains (germ fraction). It is soluble in water and stable at higher temperature and at pH lower than 5.0, but it is destroyed rapidly by boiling at pH 7.0 or above. 

Uronic acid derivatives are also known among the guanosine 5 -pyrophosphate esters. A mixture of the a-D-mannopyranosyluronic acid ester (20) and, presumably, the /J-L-gulopyranosyluronic acid ester (21) was isolated from the brown alga Fucus gardneri,88 The conversion of the uronic acid in the ester 20 into D-mannitol, and that... 

Inosine 5 -(a-D-glucopyranosyl pyrophosphate) (50) was obtained by use of the pyrophosphorylases, effective for the respective guanosine derivative, from animal tissues,50 pea,223 or Arthrobacter vis-cosus.218 The enzymic synthesis of the a-D-glucopyranosyl pyrophosphate esters of 2 -deoxyuridine223 and 2 -deoxyadenosine216 has also been described. 

A fermentation procedure has been described237,238 for large-scale production of the latter sugar nucleotide. Bakers yeast transforms guanosine 5 -phosphate into the D-mannosyl pyrophosphate ester in 45% yield when a mixture with D-glucose, potassium phosphate, and magnesium sulfate is incubated. 

The correct anomeric configuration of the a-D-glucopyranosyl pyrophosphate ester is essential (the /3-D-glucopyranosyl ester does not react),342 but the exact distance between the nucleoside moiety and the glycosyl group seems to be a less critical factor. Thus, the phosphonate analog 67 can serve as a substrate.210... 

Both mechanisms seem to be consistent with incorporation of a label from tritiated water into 101 (at C-2),412 but not into the unreacted glycosyl pyrophosphate esters,413 and also with kinetic evidence414 for liberation of the pyrophosphate 6 prior to release of 101. No requirement for added NAD has been reported, and a search for pyridine nucleotide firmly bound to the enzyme may lead to conclusive evidence for the mechanism. 

More-detailed studies of enzyme specificity towards the structure of the nucleoside residue have been performed with the sucrose synthetase of pea seedlings,339,384,501,502 and with wheat-germ arbutin synthetase.339,364,503 Neither enzyme can use the cytidine,504 isocyti-dine, or N3-methyluridine derivatives as substrates. On the other hand, the a-D-glucopyranosyl pyrophosphate esters of 4-thiouri-... 

The solvolysis of tetrabenzyl pyrophosphate catalyzed by lutidine (see above) is further catalyzed a thousandfold by calcium ions. In the presence of 0.02M calcium ion and 0.2M lutidine, the solvolysis of tetrabenzyl pyrophosphate (with cleavage of the P—O bond) is increased by a factor of the order of 1,COO,000 over the uncatalyzed reaction (63). The bivalent cation chelates with two oxygen atoms of the pyrophosphate ester, and the positive charge in the chelate greatly enhances the susceptibility of the phosphorus atom toward nucleophilic attack. 

Lewin, L.M. Brown, G.M. The Biosynthesis of thiamine. III. Mechanism of enzymatic formation of the pyrophosphate ester of 2-methyl-4-ammo-5-hy-droxymethylpyrimidine. J. Biol. Chem., 236, 2768-2771 (1961)... 

Allylie pyrophosphates. Primary allylic bromides (prepared by reaction of the alcohol with PBr3) can be converted into the corresponding pyrophosphate esters by reaction with this reagent in 46-54% overall yield (equation 1). 

In some metabolic reactions pyrophosphate esters are formed by consecutive transfer of the terminal phospho groups of two ATP molecules onto a hydroxyl... 

Allylic pyrophosphate esters.1 Allylic chlorides react with 1 in acetonitrile to provide allylic pyrophosphate esters typically in yields of 60-90% after ion-pair chromatographic purification. 

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