Enolate anion phosphorylation

In animals and in many bacteria, PEP is formed by decarboxylation of oxaloacetate. In this reaction, which is catalyzed by PEP carboxykinase (PEPCK), a molecule of GTP, ATP, or inosine triphosphate captures and phosphorylates the enolate anion generated by the decarboxylation (Eq. 13-46).252 The stereochemistry is such that C02 departs from the si face of the forming enol.253 The phospho group is transferred from GTP with inversion at the phosphorus atom 254 The enzyme requires a divalent metal ion, preferably Mn2+. 

Oxaloacetate is also decarboxylated without phosphorylation of the enolate anion formed but with release of free pyruvate. Both pyruvate kinase and PEPCK can act as oxaloacetate decarboxylases.261... 

Suelter90 has classified enzymes that are activated by monovalent cations into two groups. One involves the catalysis of phosphoryl-transfer reactions and the other a variety of elimination and/or hydrolytic reactions in which a keto-enol tautomer can be invoked as an intermediate. The M+ cation is then required to stabilize the enolate anion. It is still not possible to verify this hypothesis, but it seems unlikely in view of the comments above. 

Stabilization of enolate anions generated from abstraction of a proton a to a carboxylate Hydrolysis, phosphoryl group transfer via hydrolytic nucleophilic substitution Stabilization of diverse oxyanion intermediates via metal-assisted catalysis Schiff base dependent formation of an electron sink ... 

Protection or reductive deoxygenation of alcohols and ketones. Ireland et al.2 have found that N,N,N, N -tetramethylphosphoroiiamidates (TMPDA derivatives) of alcohols and of ketone enolates are reduced in high yield by lithium-ethylamine. They are readily prepared by phosphorylation of alcoholate or enolate anions. The complete sequence is as follows. The alcoholate anion is simply prepared by treatment of an alcohol with a slight molar excess of n-butyllitliium. The enolate anions of saturated ketones are prepared by treatment with lithium diisopropylamide. In the case of a,/J-unsaturated ketones, lithium-ammonia reduction or conjugate organometallic addition is suitable. For phosphorylation of the Jnion a fivefold excess of N,N,N, N -tetramethyldiamidophosphorochloridate in 4 ] dimethoxyethane (or THF)-N,N,-N. N -tetramethylethylenediamine (TMEDA) is used. The reaction is complete after... 

Suelter has summarized the enzymes catalysed by monovalent cations and has suggested that the data from the various reactions are consistent with a unique interaction of metal with the enzyme and substrate to form a functional ternary complex. While this complex cannot yet be uniquely defined, the pattern of activation suggests that (i) phosphorylation of a carboxy-group or enolate anion, (ii) elimination reactions resulting in a keto-enol tautomer, and (iii) other reactions in which a keto-enol tautomer can be considered as an intermediate, are all candidates for activation by a monovalent cation. 

When monomeric metaphosphate anion POf (102) is generated form the phos-phonate dianion 170 in the presence of the hindered base 2,2,6,6-tetramethylpiper-idine, it undergoes reaction with added carbonyl compounds147), Thus, it phosphoryl-ates acetophenone to yield the enol phosphate, whereas in the presence of acetophenone and aniline the Schiff base is formed from both compounds, probably by way of the intermediate C6H5—C(CH3) (OPO e) ( NH2C6HS). This reactivity pattern closely resembles that of monomeric methyl metaphosphate 151 (see Sect. 4.4.2). 

This procedure has not been seriously adopted in view of the very marked tendency of active methylene carbanions and appropriate phosphorylating agents, for example, (Et0)2P(0)Cl, to form phosphate esters derived from the enol tautomers. One useful example appears to such phosphorylation of the anions derived from the species RCH2Z, with R = H, Me, Et or prop-2-enyl, and Z = CN or COOMe (and also NO2, but not MeO) ... 

The phosphorylation of the mesomeric anion from a ketone or other active methylene compound forms a standard route to enol phosphates the process is illustrated in equation 32 with the formation of the phosphate esters 548 (R = Me or Ph, = H, COMe or... 

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