Monophosphate monoesters

Phosphate Esters. The phosphorylation of sucrose using sodium metaphosphate has been reported (78). Lyoptulization of a sodium metaphosphate solution of sucrose at pH 5 for 20 hours followed by storage at 80°C for five days produced a mixture of sucrose monophosphates. These products were isolated by preparative hplc, with a calculated yield of 27% based on all organic phosphate as sucrose monoesters. Small proportions of glucose and fmctose were also formed. 

A similar reaction mechanism was proposed by Chin et al. [32] for the hydrolysis of the biological phosphate monoester adenosine monophosphate (AMP) by the complex [(trpn) Co (OH2)]2+ [trpn = tris(ami-nopropyl)amine]. Rapid cleavage is observed only in the presence of 2 equiv metal complex. It is evident from 31P NMR spectra that on coordination of 1 equiv (trpn)Co to AMP a stable four-membered chelate complex 4 is formed. The second (trpn)Co molecule may bind to another oxygen atom of the substrate (formation of 5) and provide a Co-OH nucleophile which replaces the alkoxy group. The half-life of AMP in 5 is about 1 h at pD 5 and 25 °C. 

The H-phosphonate approach entails phosphitylation of a hydroxylic component with an activated unprotected derivative of phosphonic acid to furnish H-phosphonate (a stable tetra-coordinate form of the unprotected monophosphite) followed by oxidation on phosphorus. The H-phosphonate approach is not generally used for the synthesis of monophosphates due to the difficulty of oxidation of the H-phosphonate monoesters and the necessity either to render the phosphorus atom of H-phosphonate into the three-coordinate form by silylation (to form disilylphosphite) or to introduce a protecting group (to form H-phosphonate diester) prior to oxidation. Nevertheless, in rare cases, the H-phosphonate procedure turns out to be a method of choice if, for instance, the simultaneous oxidation of functional groups other than H-phosphonate is required.51... 

A more complex pathway of activation is seen in N-amino acid derivative of phosphoramidic acid diesters of antiviral nucleosides, as exemplified by prodrugs of stavudine (9.79, Fig. 9.14) [153 -155], The activation begins with a carboxylesterase-mediated hydrolysis of the terminal carboxylate. This is followed by a spontaneous nucleophilic cyclization-elimination, which forms a mixed-anhydride pentacycle (9.80, Fig. 9.14). The latter hydrolyzes spontaneously and rapidly to the corresponding phosphoramidic acid monoester (9.81, Fig. 9.14), which can then be processed by phosphodiesterase to the nucleoside 5 -monophosphate, and by possible further hydrolysis to the nucleoside. 

Solvolysis studies of meta- and para-substituted phenyl phosphates (240) in anhydrous Bu OH and in Am OH have revealed that generally reactions of dianions are much faster in alcohols than in water. For example, the dianion of p-nitrophenyl phosphate (240 X = 4-NO2) reacts 7500- and 8750-fold faster in Bu OH and Am OH, respectively, than in water." The results of a theoretical study of the reactivity of phosphate monoester anions in aqueous solution do not support the generally accepted view that Brpnsted coefficients fhg = —1.23 and jSnuc = 0.13 determined more than 30 years ago for the uncatalysed reaction of water and a monophosphate dianion (241) represent conclusive evidence for the dissociative mechanism. It is suggested that, instead, the observed LFERs could correspond to a late transition state in the associative mechanism." ... 

Figure 3. Effect of pH on the chemical shift of several monoester phosphate compounds. Serine phosphate and inositol monophosphate are in a pure water matrix, and adenosine monophosphate is in a concentrated humic-FeEDTA...

Venom endonuclease is 3 -monoester former with a preference for the Gp-G bond and an optimal pH of 5 (12). It represents the most dangerous contaminant of exonuclease in experiments designed for the identification of terminals in long chains bearing 3 -monophosphates because it leads to false terminals. 

The hydrolysis of adenosine 3. 5 -cyclic monophosphate (cAMP) by the cobalt complexes (215) was considered here earlier,187 as was the Ce(IV)-catalysed hydrolysis of phospho monoesters in nucleotides.189 A review (ca 100 references) on current data on the mechanism of cleavage-transesterification of RNA has appeared.258 In this review special attention was focused on the two crucial steps in the hydrolysis of RNA, i.e. cleavage-transesterification and hydrolysis of the cyclic phosphodiester (Scheme 14). The catalysis of various amines for the hydrolysis of RNA has been looked at and ethylenediamine and propane-1,3-diamine are highly active under physiological conditions because they exist as the catalytically active monocation forms.259... 

Massoud SS, Sigel H (1988) Metal coordinating properties of pyiimidine-nucleoside-5-monophosphates (CMP, UMP, TMP) and of simple phosphate monoesters, including D-ribose 5-monophosphate. Establishment of relations between complex stability and phosphate basicity. Inorg Chem 27 1447-1453... 

Inositol phosphates are often the most abundant organic phosphorus compounds in soils, although they are less common in aquatic samples. They include a sequence of phosphate monoesters, from inositol hexa-kisphosphate to inositol monophosphate (Mandal and Islam, 1979 Harrison, 1987), in various stereoisomeric configurations [myo, scyllo, neo, B-cbiro) of the sugar inositol (Anderson and Malcolm, 1974 Anderson et al., 1974 Cosgrove, 1980 Harrison, 1987 Turner et al, 2002). These compounds are... 

Benzopyrano (3,4-b) furo (2,3-h) (1) benzopyran-6 (6aH)-one, 1,2,12,12a-tetrahydro-2-a-isopropenyl-8,9-dimethoxy-. See Rotenone 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-, acetate. See dl-a-Tocopheryl acetate 2H-1-Benzopyran-6-ol, 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-, monoester with ascorbyl monophosphate, dipotassium salt. See Potassium ascorbyl tocopheryl phosphate... 

R-PO3 ) (O) 4-nitrophenyl phosphate (NPhp ), phenyl phosphate (php ), uridine S -monophosphate (UMp ), D-ribose 5-monophosphate (RibMp ), thymidine [-l-(2-deoxy-13-D-ribofuranosyl)thymine] 5 -monophosphate (dTMP ), n-butyl phosphate (Bup ), methanephosphonate (MeP ) and ethanephosphonate (EtP ) (from left to right). The least-squares lines (eq. (11)) are drawn through the corresponding 8 data sets (O) taken from ref [38] for the phosphate monoesters and from ref [5] for the phosphonates. The points due to the equilibrium constants for the M VPA systems are based on the values listed In Tables (column 4) and 2 (columns 4 or S). The vertical broken lines emphasize the stability differences from the reference lines they equal log as defined In eq. (12) for the M(PA) complexes. All the plotted equilibrium constants refer to... 

Unfortunately, charged phosphorylated or phosphonylated nucleosides are unable to penetrate the cell membranes or the blood-brain barrier because of their low lipophiUci-ty. Meier et al. [66] have described the synthesis of a new prodrug system for antiviral nucleosides AZT and ddT based on a-hydroxybenzylphosphonates 1, which present uncharged prodrugs of 5 -nucleoside H-phosphonates and 5 -nucleoside monophosphates. All compounds 1 exhibited pronounced activity against HIV-l- and HlV-2-infected cells without toxicity. Compounds 3 can be considerd as potential prodrugs of the 3 -azido-3 -deoxythimidine and 2, 3 -deoxythimidine, their H-phosphonate monoesters as well as their monophosphates. 

---