Phosphorylated amine

Method D (EtO)2PHO (6.9 g, 50 mmol) in CC14 (10 ml or 30 ml when an amine salt is used) is added dropwise with stirring to the amine or amine salt (50 mmol), KHCO, (10 g), and TBA-Br (0.8 g, 2.5 mmol) in CH2C12 (40 ml) at 10-15°C. The reaction is exothermic and requires external cooling. The mixture is stirred at 15-20°C for 2 h (4 h for the amine salt) and then allowed to stand at room temperature for 12 h. The mixture is filtered and the solid washed with CH2C12 (2 x 25 ml). The combined organic solutions are evaporated to yield the phosphorylated amine. 

The coupling of o-aroylbenzoic or nicotinic acids with phosphorylated amines using dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) followed by deprotonation with potassium bis(trimethylsilylamide) and cyclization gave isoquinolines or naphthyridinones in good yields (Scheme 43) <1996T4433>. 

Acid fluorides can be used for a elean preparation of amides.9 96 The use of silylated amines is an elegant alternative, sinee liberated fluoride progressively desilylates them to more nucleophilic species. The reaction has to be started with a catalytic amount of fluoride (TBAF).92 Stannyl amines97 or phosphoryl amines (phosphoramides)98 have been used in similar reactions. 

Alcoholysis of the phosphoryl chloride produces the bis(phosphoryl)amine ... 

Thiophosphorylation. Thiophosphoryl chloride will thio-phosphorylate amines, alcohols," amino alcohols, diols, and diamines. The rate of reaction decreases as each chlorine atom in replaced thus it is possible to replace each chlorine atom with a different substituent under controlled reaction conditions. Thiophosphoryl derivatives of chiral amino alcohols have been studied extensively as stereochemical probes for the stepwise hydrolyses and alcoholysis of thiophosphates (eq 2), which can lead to the... 

Many enzymes that mediate phosphoryl transfer from ATP are thought to do so via the formation of a phosphorylated imidazole residue of histidine (Scheme 49). Spontaneous reactions of amines with ATP are legendarily slow, but now a systematic study, involving trapping of the phosphorylated amine with F , has shown that amines (pyridines, imidazoles) react with ATP 30-100-fold faster than do water or alcohols. To complicate the interpretation of the results, it was found that the rate constant for the reaction of F with ATP tetraanion is similar to rate constants for reaction of uncharged amine and oxygen nucleophiles, thus dispelling the myth that reactions of ATP and other phosphoryl anions with anionic nucleophiles are prevented by electrostatic repulsion in aqueous solution. ... 

The largest value of membrane permeability on Nd ion is observed when using diphosphorilamine 4, whereas structurally similar carrier 1 demonstrates the lowest permeability value on this ion. As for Sm , its permeability appears as the highest and approximately similar when transporting by means of mono phosphorylated amines 2 and 1 Sc is transported by means of amino phosphine oxide 2 with less efficiency, and chemical agent 3 demonstrates the largest efficiency for it. 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

Monsanto has disclosed the use of carbon dioxide—amine complexes which are dehydrated, at low temperatures, with phosphoryl chloride [10025-87-3] or thionyl chloride [7719-09-7] as a viable route to a variety of aUphatic isocyanates. The process rehes on the facile formation of the intermediate salt (30).REPLACEVariations of this process, in which phosgene is used as a dehydrating agent, have been reported earlier (84). Table 2 Hsts commercially available aUphatic isocyanates. 

The biochemical basis for the toxicity of mercury and mercury compounds results from its ability to form covalent bonds readily with sulfur. Prior to reaction with sulfur, however, the mercury must be metabolized to the divalent cation. When the sulfur is in the form of a sulfhydryl (— SH) group, divalent mercury replaces the hydrogen atom to form mercaptides, X—Hg— SR and Hg(SR)2, where X is an electronegative radical and R is protein (36). Sulfhydryl compounds are called mercaptans because of their ability to capture mercury. Even in low concentrations divalent mercury is capable of inactivating sulfhydryl enzymes and thus causes interference with cellular metaboHsm and function (31—34). Mercury also combines with other ligands of physiological importance such as phosphoryl, carboxyl, amide, and amine groups. It is unclear whether these latter interactions contribute to its toxicity (31,36). 

An alternative method involves reaction of an a-acylaminoketone (12) with a primary amine and subsequent ring closure of the resultant Schiff s base (13) with phosphoryl chloride. This enables the introduction of a 1-substituent as in (14) to be carried out efficiently, and if the amine were replaced with a monosubstituted hydrazine, the imidazole derivative (IS) resulted (78LA1916). 

The decomposition of (536) with hydrogen sulfide yields pyrazole (76T1909). The 1-phosphorylpyrazoles (537) are suitable reagents for the phosphorylation of alcohols, amines, hydrazines and azides (76AG(E)378). 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Phosphatidylethanolamine synthesis begins with phosphorylation of ethanol-amine to form phosphoethanolamine (Figure 25.19). The next reaction involves transfer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate. As always, PP, hydrolysis drives this reaction forward. A specific phosphoethanolamine transferase then links phosphoethanolamine to the diacylglycerol backbone. Biosynthesis of phosphatidylcholine is entirely analogous because animals synthesize it directly. All of the choline utilized in this pathway must be acquired from the diet. Yeast, certain bacteria, and animal livers, however, can convert phosphatidylethanolamine to phosphatidylcholine by methylation reactions involving S-adenosylmethionine (see Chapter 26). 

This amide, readily formed from an amine and the anhydride or enzymatically using penicillin amidase, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides, phosphorylated peptides, and oligonucleotides, as well as on nonpeptide substrates. The deprotection of racemic phenylacetamides with penicillin acylase can result in enantiomer enrichment of the cleaved amine and the remaining amide. An immobilized form of penicillin G acylase has been developed. ... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

Quinazolin-4(3/7)-one was converted into 4-chloroquinazoIine on heating with a mixture of phosphoryl chloride and phosphorus pentachlo-ride [80IJC(B)775], Phosphoryl chloride in the presence of triethylamine, however, transformed quinazolin-2,4(lf/,3//)-dione into 2-chloro-4-diethylaminoquinazoline. More bulky amines allowed formation of the 2,4-dichloro derivative (82CPB1947). 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

Thioacylation of primary and secondary amines, including aminoacids and aminoalcohols, has been readily carried out from phosphonodithioacetate 28 (R = Et) and the resulting phosphorylated thio amides (thio carbamoyl-... 

PreUminary studies on the racemic reaction of protected imines with ni-tromethane showed that the thiourea and the amine mutually weakened their reactivities. However, the bifunctional amino-thiourea led to good results. Enantioselectivity of the adduct depended on the protecting group, P(0)Ph2 affording the best results (76% ee). Then, other aromatic imines substrates were successfully phosphorylated with good to high enantioselec-tivities (63-76% ee). 

Oxidation and amination of IMP forms AMP and GMP, and subsequent phosphoryl transfer from ATP forms ADP and GDP. Further phosphoryl transfer from ATP to GDP forms GTP. ADP is converted to ATP by oxidative phosphorylation. Reduction of NDPs forms dNDPs. 

Product Acceptors. Many enzyme assays use acceptors, as for instance 2-ethylaminoethanol and other aminated alcohols iihich act as acceptors for the phosphoryl product of the reaction catalyzed by alkaline phosphatase (25) (Fig. 4). Hydroxylamine can act as an acceptor for the hydroxyacetone produced by eno-lase and semicarbazide can act as an acceptor for the pyruvate produced by LD. It is necessary to optimize the concentration of such an acceptor before using it routinely as often what may be a theoretically desirable acceptor is in practice superfluous. 

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