Uridine 3-methyl-, 3 -phosphate

The possibility that, during the alkaline hydrolysis of ribonucleic acid, tri-esters (18) - could be intermediates was ruled out on mechanistic groxmds."f > Furthermore, it was shown that the tri-ester, uridine 2 3 -(methyl phosphate) (18, R = CH3), synthesized by methylation of uridine 2 3 -cychc phosphate with diazomethane, is resistant to ribo-nuclease. f However, it has been observed that, when the benzyl ester of cytidylic acid 6 is partially hydrolyzed in acid, a significant proportion of the o isomer of this phosphoric diester is formed." ) In addition, the dinucleoside phosphates, such as adenylyl-(3 —>5 )-cytidine (14a), are also isomerized to the corresponding (2 - 5 )-dinucleoside phosphates by treatment with acid. " These studies suggest that cyclic triesters (or derivatives thereof) may be intermediates in isomerization of these phospho-diesters in acidic mediiun. 

A conformational study of nucleic acid phosphate esters has been carried out using n.m.r. and the temperature-dependent chemical shifts used to give information about the geometry of the phosphodiester linkage. Compounds studied were 3 - and 5-O-methyl phosphates of uridine and adenosine, and the 3-0-methyl phosphate of 6-A-dimethyladenosine. It has been reported that the n.m.r. of myo-inositol hexakisphosphate has four resonances that shift and broaden as a function of pH. ° Reference to the use of P n.m.r. in the configurational determination of cyanomethyl-branched phosphonates is made in Chapter 16. 

Nucleosides, Nucleotides, Derivatives, and Related Compounds. — 5-Substituted uracils were examined for conformational dependence on the substituents, uridine 5 -phosphate disodium salt, 2 -deoxyuridine 5 -phosphate disodium salt, " 6-methyl-2 -deoxyuridine, 5-C-acetyl-2 -deoxyuridine, dihydrouridine 3 -phosphate potassium salt, 5-hydroxymethyl-2 -deoxyuridine, 4-thio--uridine, 2,5 -anhydro-2, 3 -0-isopropylidene-2-thiouracil, 2,2 -an-hydro-1 - 3-D-arabinofuranosyl-2-thiouracil. ... 

Leulliot N, Ghomi M, Scalmani G, Berthier G (1999) Ground state properties of the nucleic acid constituents studied by density funetional calculations. I. Conformational features of ribose, dimethyl phosphate, uridine, eytidine, 5 -methyl phosphate-uridine, and 3 -methyl phosphate-uridine. J Phys Chem A 103 8716-8724. doi 10.1021/jp9915634 Leulliot N, Ghomi M, Jobie H et al (1999) Ground state properties of the nucleic acid constituents studied by density funetional calculations. 2. Comparison between calculated and experimental vibrational speetra of uridine and eytidine. J Phys Chem B 103 10934-10944. doi 10.1021/jp9921147... 

The substituents at the 5 or 6 position of the pyrimidine base have no relation to the susceptibility to RNase T2. Madison and Holley 93) have shown that RNase T2 is able to split the phosphodiester bonds of pseudouridylic acid and 5,6-dihydrouridylic acid. Recently, Saneyoshi et al. 86) have found a new minor constituent, Vp, with 5-methyl cytidine 3 -phosphate and other mononucleotides on the two-dimensional paper chromatogram of RNase T2 exhaustive digest of E. coli tRNAVal later the structure of V was proved to be uridine-5-oxyacetic acid 94). 

Figure 4 Coenzymes of methanogenesis. F-430, coenzyme M (2-thioethanesulfonate), and coenzyme B (7-thioheptanoyl-threonine-O-phosphate [sometimes abbreviated HS-HTP]). Methyl-reducing factor is a structure proposed on the basis of NMR and mass spectrometry, in which the phosphate group of CoB is linked by a carboxylic-phosphoric anhydride to a UDP disaccharide, uridine 5 -(2-acetamido-2-deoxymannopyranuronosyl)-2-acetamido-2-deoxy-glucopyranosyl-diphosphate [171]. The CoB moiety without it appears to be functionally active in the enzyme reaction.

Different types of substitution/conversion-editing have been described. The best characterised involves cytidine deamination to uridine in the editing of transcripts for apolipoprotein B, and adenosine deamination to inosine in the editing of the transcripts encoding the glutamate receptor subunits. More than 90 different types of base modifications have been described. Moreover, methylations and substitutions of the ribose and phosphate moieties have also been identified. Recently, the 2 -0-ribose methylation has been the focus of much attention since the discovery that the snoRNA guides the methylation in a frans-acting fashion. 

As pyrimidine nucleosides are rather stable under acidic conditions, they may be phosphorylated with a mixture of 85% phosphoric acid and phosphorus pentaoxide ( polyphosphoric acid )- The 2, 3 -0-isopropylidene acetals of uridine and of cytidine were treated with polyphosphoric acid for two hours at 60°. After acid hydrolysis, the 5 -phosphates of these nucleosides were obtained in good yield. 2, 3 -0-Benzylidenecytidine was phosphorylated similarly to cytidine 5 -phosphate. The polyphosphoric acid method was also used to convert the 2, 3 -0-isopropylidene acetals of 5-bromouridine, 3-methyluridine, and A -methyl- and A -dimethyl-cytidine into their respective nucleoside 5 -phosphates. 

Hydrogenation of methylated uridylic acids with platinum oxide is rather sluggish. However, satisfactory reduction of the 2 (3 )-phosphates of uridine and cytidine was accomplished by Cohn and Doherty, who introduced the use of 5% rhodium-on-alumina in these hydrogenations it was from such studies that chemical proof of the position of the phosphoric group in the a and 6 isomers of uridylic and cytidylic acid (see... 

Chemical Synthesis.—Purine nucleoside 5 -monophosphates enriched with or 0 on the phosphate group are conveniently prepared by treating phosphorus pentachloride in dry triethyl phosphate with one equivalent of the appropriately labelled water to give PO]- or P 0]P0Cl3, which is not isolated but mixed with adenosine or guanosine in the same solvent. Work-up of the resulting 5 -phos-phorodichloridate in similarly labelled water permits the formation of pO]-or P 0]AMP (or GMP) in fair yield with good enrichment. The 5 -monophos-phates of the 5 -C-methyl uridines derived from 6-deoxy-D-allose and 6-deoxy-L-talose have been prepared via phosphorylation of the 2, 3 -0,0-ethoxymethyl-idene derivative of the nucleosides (1) with -cyanoethyl phosphate and DCC or TPS-Cl. The same method has been used to phosphorylate iV -benzoylated 2, 3 -0,C -isopropylidene derivatives of various 5 -C-alkyladenosine species (2) and also 4 -allyladenosine (3) as part of a study in which derivatives of AMP... 

Syntheses involving standard condensation procedures for heterocyclic bases with amino-sugar derivatives have included the preparation of 2 -azido-, 3 -azido-2 ,5 -diazido-, and 3, 5-diazido-derivatives of arabino-nnAinc, 3 -amino-3-deoxy-adenosine, -uridine, and -cytidine 5-phosphates, 2, 3-bis(2-chloroethyl)-aminophosphoryl-3-amino-3-deoxyadenosine (which has anti-tumour activity), 3-A -methyl-A -nitrosoureido-3-deoxy-adenosine and the corresponding 5-substituted isomer, and 2 -azido-2-deoxy- and 2-amino-2-deoxy-D-arabinofuranosyl-... 

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