Pyrophosphate formation

This interesting conversion of a five- into a six-membered heterocyclic ring was proven by the isolation of the enzyme GTP-cyclohydrolase from E. coli (71MI21600) and a similar one from Lactobacillus platarum (B-71MI21601) which catalyzes the reaction (300)(303). Dephosphorylation leads to 7,8-dihydro-D-neopterin (304), which is then cleaved in the side-chain to 6-hydroxymethyl-7,8-dihydropterin (305), the direct precursor of 7,8-dihy-dropteroic acid and 7,8-dihydrofolic acid (224). The alcohol (305) requires ATP and Mg " for the condensation with p-aminobenzoic and p-aminobenzoylglutamic acid, indicating pyrophosphate formation to (306) prior to the substitution step. 

H. Baltscheffsky, L.-V. von Stedingk, H. W. Heldt and M. Kligenberg (1966). Inorganic pyrophosphate formation in bacterial photophosphorylation. Science, 153, 1120-1122. 

The BOP- or PyBOP-mediated SPPS of phosphinot or phosphono peptides can be carried out without protecting the phosphinic or phosphonic acid group. Indeed, phosphinic acids are activated, but the P—N bond is not formed. Phosphonic acids are also acti-vatedt and in fact an amide of methyl phenylphosphonic acid has been obtained, however, in the case of protected a-amino phosphonic acids, phosphonamides are only obtained by using AT-phthalyl protection. Side-chain unprotected phosphorylated tyrosine [Tyr(P03H2)] can be coupled by solid-phase synthesis using BOP (PyBOP), but pyrophosphate formation is also observed and some particular Tyr(P)-peptide syntheses are prone to total failure. ... 

However, the Japanese group has noted partial cleavage of the diisopropylsi-lanediyl linkage under the acidic conditions needed for the DMTr group removal [245, 247]. To circumvent this nuisance, Kobori et al. [247] have prepared a highly cross-linked polystyrene-supported phenyldiisopropylsilyl ether linker that proved to be completely stable to detritylation and used it successfully for oligonucleotide synthesis without N-protection by O-selective phosphoramidite chemistry [246] and pyrophosphate formation on solid phase [248]. The anchor can be cleaved under almost neutral conditions by 1M TBAF-AcOH in THF (90% release after 1 h) or 0.2 M triethylamine trihydrofluoride in the presence of 0.4 M triethylamine for 4h. 

MIO. Mori, Y., Nagamine, K., Tomita, N., and Notomi, T., Detection of loop-mediated isothermal amplification reaction by turbidity derived from magnesium pyrophosphate formation. Biochem. Biophys. Res. Commun. 289, 150-154 (2001). 

Infrared spectra of hydroxyapatite (Ca,o(P04)6(OH)2), octacalcium phosphate (CagH2(P04)6-5H20X and pyrolyzed octacalcium phosphate have been studied by Fowler et al. (1966). They investigated by means of infrared techniques, weight loss of sample, and pyrophosphate analysis the conditions under which pyrophosphate formation according to either of the following two reactions would be sufficiently quantitative so that it could be used to measure the amount of octacalcium phosphate in an apatitic sample ... 

Adenosine 5 -triphosphate (ATP) hydrolyzes via the diphosphate (rate constant k ) and monophosphate ( 2)) ot directly to the monophosphate with the pyrophosphate formation (k ). One mole of pyrophosphate then hydrolyzes to 2 mol of phosphate ( 4) ... 

Fig. 18.4. Origin and stereochemistry of isopentenyl pyrophosphate and dimethylallyl pyrophosphate formation.

Formation of Geranylgeranyl Pyrophosphate Formation of Prephytoene Pyrophosphate Formation of Phytoenes Acyclic Carotenoids Alicyclic Carotenoids Oxygenated Carotenoids Site of Synthesis Chemosystematic Studies Carotenoids in Algae Cartenoids in Fungi Biological Activity... 

The D Souza and Bender system shows many of these features. Systems that induce bond formation require the presence of several binding and reactive groups. The catalytic molecule should act as a co-receptor bringing together reactant, substrate and intermediate complex. As an example, Hisselni and Lehnl l demonstrated pyrophosphate formation from the intermediate phosphoramidate formed by phosphorylation of the macrocycle by ATP. In a second reaction step, the phosphoramidate reacts with a phosphate group to form pyrophosphate (see Fig. 7.10). 

No pyrophosphate formation was observed in the absence of metals under these experimental conditions. 

An alternative synthesis, which eliminates pyrophosphate formation, promotes cyclization by generation of a potent alkoxide nucleophile. The base used for this purpose is one of the most potent known potassium tert-butoxide in dimethyl sulfoxide. Of course, the presence of a good leaving group is also necessary ... 

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