Phosphoric anhydride synthesis

FIGURE 11.15 Formadoii of ADP and ATP by the successive addition of phosphate groups via phosphoric anhydride linkages. Note the removal of equivalents of H9O in these dehydration synthesis reactions. 

In both cases, the mixed anhydride is used to synthesize ATP from ADP. Hydrolysis of the anhydride liberates more energy than the hydrolysis of ATP to ADP and, therefore, can be linked to the enzymic synthesis of ATP from ADP. This may be shown mechanistically as a hydroxyl group on ADP acting as nucleophile towards the mixed anhydride, and in each case a new phosphoric anhydride is formed. In the case of succinyl phosphate, it turns out that GDP rather than ADP attacks the acyl phosphate, and ATP production is a later step (see Section 15.3). These are enzymic reactions therefore, the reaction and the nature of the product are closely controlled. We need not concern ourselves why attack should be on the P=0 rather than on the C=0. 

In the particular case of the synthesis of the 14-member i polyoxomacrolide narbonolide, direct cyclization through the activation of thiol ester failed and then the mixed phosphoric anhydride derived from diphenylphosphorochloridate was developed to effect cyclization by Masamune and coworkers [39]. Fukumoto et al. [40] applied this procedure to the synthesis of the macrocyclic alkaloid vertaline 63). Thus, seco acid 62 was treated with diphenyl phosphorochloridate and triethylamine followed by refluxing in benzene in the presence of DMAP at high dilution afforded 63 in 54% yield (Scheme 20). 

Another useful reagent for macrolactonization via mixed phosphoric anhydride is N,N- bis(2-oxo-3-oxazolidinyl)phosphordiamidic chloride (BOP-Cl, 64), which was used by Corey and coworkers [41] in the first synthesis of aplasmomycin (67), a novel boron-containing macrocyclic antibiotic. As shown in Scheme 21, the linear precursor 65 was treated with 3 equiv of BOP-Cl (64) and 7 equiv of triethylamine in dichloromethane at 23 °C for 6 h to give the dilactone 66 in 71% yield. 

Red phosphorus (RP) is a component of matchbox strike plates and is used as an ingredient in certain commercial rat and cockroach poisons. RP is used in the manufacture of pyrotechnics, semiconductors, fertilizers, incendiary shells, smoke bombs (in combination with butyl rubber), and tracer bullets. It is also used in organic synthesis reactions and in the manufacture of phosphoric acid, phosphine, phosphoric anhydride, phosphorus pentachloride, phosphorus trichloride, and in electroluminescent coatings. RP (2-10%) is also used as a flame-retardant additive for plastics such as polyamides. 

Despite wide variations of synthesis conditions, the treatment of cellulose with dimethylphosphite, monomethylphosphite and phosphorous acid failed to yield phosphites containing only one type of phosphorus-containing groups. This difficulty was overcome by using phosphoric anhydrides as the esterifying reagents. The action of mixed anhydrides of phosphorous acids and acetic acid on cellulose has yielded cellulose esters with alkyl-(methyl-)phosphorous acid (73) ... 

USE White phosphorus manuf rat poisons for smoke screens, gas analysis. Red phosphorus pyrotechnics manuf safety matches in organic synthesis manuf phosphoric acid, phosphine, phosphoric anhydride, phosphorus pencachlo-ride, phosphorus trichloride manuf fertilizers, pesticides, incendiary shells, smoke bombs, tracer bullets. 

How does an organism ensure that glycogen synthesis and glycogen breakdown do not operate simultaneously If this were to occur, the main result would be the hydrolysis of UTP, which would waste chemical energy stored in the phosphoric anhydride bonds. A major controlling factor lies in the behavior of glycogen phosphorylase. This enzyme is subject not only to allosteric control but also to another control feature covalent modification. We saw an earlier example of this kind of control in the sodium-potassium pump in Section 8.6. In that example, phosphorylation and dephosphorylation of an enzyme determined whether it was active, and a similar effect takes place here. 

Dialkyl H-phosphonates are used not only for the preparation of N-protected amino acids, but also as active coupling agents in the peptide synthesis [89,115,116], Among a wide variety of methods for the synthesis of peptides, the procedure via mixed carboxylic-phosphoric anhydride-type intermediate has so far attracted attention because this compound plays an important role in the biosynthesis of proteins and peptides [117]. Zhao et al. [89] offer the following reaction scheme for the synthesis of peptides. Phenylalanine and tryptophane are nsed as amino acids. 

The chemistry of brazilin (21) and hematoxylin (22) has been reviewed by Robinson (62, 63) and Donnelly (20). In the first successful approach to a synthesis of brazilin the trimethyl ether (79) of an-hydrobrazilin (deoxybrazilone) (78) was prepared by treating 7-methoxy-3(3,4-dimethoxybenzyl)chroman-4-one (77) with phosphoric anhydride (16). The hydroxyl group at C-6a was introduced by a series of transformations (63). Later Kirkiacharian (41) found that hydration of the double bond can be achieved more directly by sequential treatment with diborane and alkaline hydrogen peroxide. The brazilin and hematoxylin derivatives obtained in this fashion were identical with products of earlier experiments. The course of the hydroboration reaction established the cis-fusion of rings B and C. 

On the basis of exchange studies a uridyl-enzyme intermediate has been postulated in the synthesis of UDP-glucose (S41S). The same type of intermediate might be common to all of the reactions in which nucleotide-phosphoric anhydrides are formed. 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

Synthesis. Hydroxyhydroquiaone is not produced on a large scale, but many uses for it are being developed. The most convenient preparation of hydroxyhydroquiaone is the reaction of -benzoquiaone with acetic anhydride ia the preseace of sulfuric acid or phosphoric acid. The resultant triacetate (29) can be hydrolyzed to hydroxyhydroquiaone (86). 

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

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. 

The solids analysis described above can be taken to yet another level by correlating the color measurement to chemical properties. An excellent model system is vanadium pyrophosphate (VPO), which is a well-known catalyst for butane oxidation to maleic anhydride. During the synthesis of the catalyst precursor, solid V2O5 particles are dispersed in a mixture of benzyl alcohol and i-butanol. In this slurry phase, the vanadium is partly reduced. Addition of phosphoric acid leads to a further reduction and the formation of the VPO structure. With a diffuse reflectance (DR) UV-vis probe by Fiberguide Ind., the surface of the suspended solid particles could be monitored during this slurry reaction. Four points can be noted from Figure 4.4 ... 

Each new double helix is comprised of one strand that was part of the original molecule and one strand that is newly synthesized. Not surprisingly, this is a very simplistic description of a quite complex process, catalysed by enzymes known as DNA polymerases. The precursors for synthesis of the new chain are the nucleoside triphosphates, dATP, dGTP, dTTP, and dCTP. We have already met ATP when we considered anhydrides of phosphoric acid (see Box 7.25) these compounds are analogues of ATP, though the sugar is deoxyribose rather than ribose. 

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