Phosphorylation reagents

The ideal phosphorylating reagents for phosphodiester syntheses should meet the following criteria ... 

The extent to which 151 phosphorylates the aromatic amine in the phenyl ring is highly dependent upon the solvent. For instance, aromatic substitution of N-methylaniline is largely suppressed in the presence of dioxane or acetonitrile while pho.sphoramidate formation shows a pronounced concomitant increase. The presence of a fourfold excess (v/v) or pyridine, acetonitrile, dioxane, or 1,2-di-methoxyethane likewise suppresses aromatic substitution of N,N-diethylaniline below the detection limit. It appears reasonable to assume that 151 forms complexes of type 173 and 174 with these solvents — resembling the stable dioxane-S03 adduct 175 — which in turn represent phosphorylating reagents. They are, however, weaker than monomeric metaphosphate 151 and can only react with strong nucleophiles. 

On use of N,N -dicyclohexylcarbodiimide instead of sulfonyl chlorides as condensation reagent in oligonucleotide synthesis, then the pyro-, tri- and tetraphosphate stages are again involved 124). The metaphosphate 183 a is found in small amounts by 3iP-NMR spectroscopy, but again no cyclic trimetaphosphate 184 can be detected, which would also be a possible phosphorylation reagent. 

Diphenyl phosphorochloridate is one of the most widely employed phosphorylating reagents for the preparation of phosphomonoesters (Scheme 3.17a).94 The chloride acts as a leaving group that can be displaced by hydroxyls. The phenyl groups act as protecting groups that... 

For instance, IGOR can be ordered to produce all five-membered cyclic molecules with the empirical formula C2H N 0 , where the atoms have their customary valence schemes. The valence isomers of cvclooctatetraene (ref. 11, 12), the 1.3-dipoles (ref. 12), and the 278 conceivable five-membered cyclic phosphorylating reagents (ref. 12) have been generated by IGOR in this operating mode (Fig. 7.6). 

Equal stimulations are observed when turnover of the ATP synthase is induced by the presence of the phosphorylation reagents leading to ATP synthesis, or by a dissipative turnover, in the presence of arsenate in place of inorganic phosphate, for example. 

VAN BOOM Phosphorylating reagent Phosphorylation of sugars or nucleosides by means of ssflcytehloiophospite 2. 

Correlation of the P NMR chemical shift with the position of bond critical points (BCP) in 0,0-dialkyl O-aryl phosphorothionates has been reported. The first isolable dialkyl iodophosphates were obtained by iodination of bis-(hexa-fluoroisopropyl)phosphites with NIS. Reactions of vinyl phosphites (19) with iodine produce dealkylated intermediates, the highly reactive phosphoroiodi-dates (20) which are efficient phosphorylation reagents to prepare biologically relevant vinylphosphates (21) (Scheme 2). ... 

Similarly, treatment of ynones with DECP and LiCN leads to the corresponding cyanophosphate, which, on reaction with cuprates in THF at low temperature, give the allenic nitrile by elimination of phosphate. Only a few reports describe the properties of DECP as a phosphorylation reagent for imidazoline nitrogen atoms, phenols, and Grignard reagents. ... 

AW -Diphenylphosphorodiamidic chloride has been recommended as a convenient phosphorylating reagent for the preparation of nucleoside 3 -phosphates since it is stable, it gives very high yields, and the resulting esters... 

In practice, for most synthetic applications, either acetyl phosphate/acetate kinase or phosphoenolpyruvate/pyruvate kinase are used to regenerate ATP. Because of the ease of preparing AcP, AcP/AcK is the most economical method for large-scale work. Its application is, however, limited to fast phosphorylation reactions where the hydrolysis of AcP is not important. The PEP/pyruvate kinase system is used in instances where the requirement for a strong, stable phosphorylating reagent outweighs the relative inconvenience of preparation of PEP. 

The mechanism for converting mevalonic acid into mevaionyi phosphate is essentially an Sn2 reaction with an adenosyl pyrophosphate leaving group (Section 27.3). A second Sn2 reaction converts mevaionyi phosphate to mevaionyi pyrophosphate. ATP is an excellent phosphorylating reagent for nucleophiles because its phosphoanhydride bonds are easily broken. The reason that phosphoanhydride bonds are so easily broken is discussed in Section 27.4. 

Phosphorylation is one of the most crucial steps in the synthesis of polynucleotides by the triester approach. We developed bis(triazolyl)p-chloro rtienylphosi ate as a powerful phosphorylating reagent, which is apparently a doubly activated reagent with triazole but will give only a diesterified product thus the formation of 3 -3 and 5 -5 dimer formation is avoided. 

The B-halogenated protective groups that can be removed by Co(I)-phthalocyanine anion, [PcCo] (refs. 6,7) and the highly reactive five-membered cyclic phosphorylating reagents (refs. 3,4,8) are the chemical basis of our attempts to contribute to the preparative methodology of oligonucleotides. ... 

The use of phosphorylating reagents of P(V) instead of the currently popular P(III) reagents would have the advantage that more stable intermediates could be expected, and that no oxidation step would be needed. 

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