Phosphoric acid mixed anhydride

Amino Acid-Phosphoric Acid Mixed Anhydrides. 100... 

Several systems based on the potentialities of amino acid-phosphoric acid mixed anhydrides have been devised to check the idea that the genetic code developed from an early pathway of RNA-dependent peptide synthesis in an RNA world [168]. RNA sequences have thus been selected that are capable of self-aminoacylation using amino acid adenylates, catalyzing a reaction chemically similar to the aminoacylation of fRNA by the protein aminoacyl fRNA synthetases [169]. 

Intermediate 113 was transformed into the trimethylsilyl methyl ketone 119 in quantitative yield via the acid chloride, followed by the addition of trimethylsilylmethyl lithium (Scheme 2.13). Subsequent Peterson olefination of aldehyde 108 with 119 resulted in the required unsaturated ketone 120 in 95% yield. Subsequent desilylation and thioester hydrolysis afforded a 97% of the seco acid 121. Lactonization was achieved in 32% yield via the phosphoric acid-mixed anhydride, however this procedure also formed about 25% of the dimeric bis lactone. Following removal of the acetonide under the action of acid, a nonselective oxidation with RuCl2(Ph3P)3 produced a 1 1 mixture of the natural... 

Masamune et al. [42] developed the macrolactonization of to-hydroxy r-butyl thioester with Hg(OCOCp3)2 in MeCN at room temperature, and this method accomplished the first total synthesis of methynolide [1]. They further developed an alternative method using a phosphoric acid mixed anhydride, which was apphed to the synthesis of narbonolide [43] and tylonolide [44]. 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

Scheme 9.6. A cartoon representation of the enzyme (named glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12) catalyzed oxidation of the aldehyde glyceraldehyde-3-phosphate to the carboxylic acid-phosphoric acid mixed anhydride, 1,3-bisphosphoglycerate (which can be hydrolyzed to the corresponding carboxyhc acid and phosphoric acid). Start in a clockwise direction from the npper left.

An intramolecular phosphoric-carboxylic mixed anhydride has been proposed to explain the specific behavior of AT-(dialkylphosphoryl)amino acids 15 that spontaneously give oligopeptides upon standing in various solvents [115]. Peptide formation was accompanied by diester exchange on the phosphoryl group via a reaction that may have been useful for nucleotide ligation. 

Aminoacyl-AMP is a mixed anhydride of a carboxylic acid and a phosphoric acid. Because anhydrides are reactive compounds, the free-energy change for the hydrolysis of aminoacyl-AMP favors the second step of the overall reaction. Another point that favors the process is the energy released when pyrophosphate (PPj) is hydrolyzed to orthophosphate (Pj) to replenish the phosphate pool in the cell. 

The 7 glutamyl phosphate formed m this step is a mixed anhydride of glutamic acid and phosphoric acid It is activated toward nucleophilic acyl substitution and gives glutamine when attacked by ammonia... 

The use of dehydrating agents such as sulfuric or phosphoric acid on (555 X = OH) was also successful, and these closures may proceed via mixed anhydrides 67AHC(8)277, 75MIP41600). Carbonyldiimidazole effected the conversion of hydroxamic acid (557) into a 3-hydroxy-1,2-benzisoxazole derivative (79JHC1277). The mixed anhydride (558) where... 

FIGURE 23.4 A mechanism for the pyruvate carboxylase reaction. Bicarbonate must be activated for attack by the pyruvate carbanion. This activation is driven by ATP and involves formation of a carbonylphosphate intermediate —a mixed anhydride of carbonic and phosphoric acids. (Carbonylphosphate and car-boxyphosphate are synonyms.)... 

The combination of copper salts and snlfnric acid is another widely used charring reagent. For preparation, 10 ml of concentrated H2SO4 has to be mixed carefully with 90 ml of acetic anhydride. Three grams of copper-II-acetate is dissolved in 100 ml of 8% phosphoric acid. After plate dipping or plate spraying, 15 min of heating at 125°C is recommended [17]. 

Carboxylic acids can also be activated by the formation of mixed anhydrides with various phosphoric acid derivatives. Diphenyl phosphoryl azide, for example, is an effective reagent for conversion of amines to amides.140 The proposed mechanism involves formation of the acyl azide as a reactive intermediate. 

Several successful cyclizations of quite complex structures were achieved using polyphosphoric acid trimethylsilyl ester, a viscous material that contains reactive anhydrides of phosphoric acid.58 Presumably the reactive acylating agent is a mixed phosphoric anhydride of the carboxylic acid. 

The condensation reactions are preferentially carried out in pyridine. As reactive species for phosphorylation of the nucleoside R OH (synthesis of a phosphortriester), the phosphoric acid azolide has been assumed. The mixed phosphoric sulfonic anhydride and a pyrophosphate tetraester have been suggested as intermediates leading to the phosphoric acid azolide. 

Mixed Anhydrides of Phosphoric, Phosphonic, and Phosphinic Acids with Sulfonic Acids... 

Mixed anhydrides between phosphoric, phosphonic, and phosphinic acids on one side and sulfonic or carboxylic acids on the other are conveniently prepared via phosphor-azolides.[150]... 

Imidazolesulfonic acid reacts with phosphinic and phosphoric imidazolides to give mixed anhydrides of the following type 1501... 

Acylphosphates mixed anhydrides of phosphoric and carboxylic acids... 

As we consider biochemical processes in Chapter 15, we shall encounter some metabolic intermediates that are acylphosphates, i.e. hybrid mixed anhydrides of phosphoric and carboxylic acids. The simplest example of an acylphosphate is acetylphosphate, employed by some bacteria as an energy-rich metabolite. 

The intermediate aminoacyl-AMP can also be seen to be an anhydride, but in this case a mixed anhydride of carboxylic and phosphoric acids (see Box 7.27). This can react with a hydroxyl group in ribose, part of... 

If we look at the structure of 1,3-diphosphoglycer-ate, we can see that it is actually an anhydride, albeit a mixed anhydride of a carboxylic acid and phosphoric acid (see Box 7.27). Accordingly, we expect it to... 

Compounds of one acid with another are referred to as acid anhydrides. A particularly large amount of energy is required for the formation of an acid—anhydride bond. Phosphoric anhydride bonds therefore play a central role in the storage and release of chemical energy in the cell (see p. 122). Mixed anhydrides between carboxylic acids and phosphoric acid are also very important energy-rich metabolites in cellular metabolism. 

As it is probable that the equilibria between the two acids and the three anhydrides are established in reactions of relatively low velocity, the distillation must be carried on very slowly, in spite of the catalytic action of the phosphoric acid. The intermediate fractions contain the mixed anhydride, detectable by its odor, which resembles that of acetophenone. 

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