Purines ribosyl

Ribosylation of uracils is usually carried out via bis-silyl derivatives and is subject to the same stereochemical difficulties as purine ribosylation (for further discussion see section 23.2.1.2). 3-Pyridazinones alkylate cleanly on N-2 under phase-transfer conditions but the regiochemistry of uracil alkylation is sometimes difficult to control. 

P2j Z = 2 D = 1.57 R = 0.048 for 931 intensities. The base exists in the thioxo form, with C-8=S and N-7 protonated. The 8-thio substituent causes the base to assume the syn (—102.6°) orientation. The o-ribosyl group is 2T3 (174.8 °, 44.1 °). The exocyclic, C-4 -C-5 bond orientation is trans (—173.2°). This does not favor intramolecular hydrogen-bonding of 0-5 to N-3 of the syn base. The C=S distance is 166.8 pm. The S atom is involved in a weak, acceptor hydrogen-bond to a water molecule, S H-O(w) = 361 pm. The bases are stacked head-to-tail, with overlap of the C=S bonds and the purine ring, in contrast to the known, related structure l-/ -D-ribofuranosyl-2-thioxo-3ff-benzimidazole,197 where similar head-to-tail stacking of the bases involves overlap of the base rings only. 

P212121 Z — 8 Dx= 1.57 R = 0.085 for 1,743 intensities. The two independent molecules have similar conformations. The glycosyl dispositions are anti (90.1°, 91.2°), and the D-ribosyl groups are 3T4 (24.0°, 34.1° 15.6°, 35.5°). The exocyclic, C-4 -C-5 bond orientations are gauche+ (63.1°, 53.8°). The orientation of the methyl groups in both molecules is such that it is directed away from the imidazole moiety of the base, that is, the 0-6-C-7 bond is trans to the C-5-C-6 bond this arrangement constitutes an obstacle to formation of Watson-Crick hydrogen-bonds to the complementary base cytosine. In molecule A, 0-6 and C-7 are displaced from the purine plane by 79 and 87 pm, and, in molecule B, by 49 and 16 pm. The bases are stacked. 

P2J2A Z = 8 Dx = 1.931 R = 0.034 for 2,321 intensities. There are two molecules in the asymmetry unit, and both exhibit the syn disposition (—84.5°, + 76.1°) for the base. The conformation of the D-ribosyl group is 3T4 (28.5°, 39.4°) in molecule A and 3T2 (359.9°, 36.2°) in molecule B. The exocyclic, C-4 -C-5 bond torsion-angle is gauche+ for both molecules (55.2°, 59.7°). The purine bases of the crystallograph-ically independent molecules are paired by N-l-H 0-6 hydrogen bonds across a pseudo-two-fold axis. The bases are stacked such that the Br atoms are tucked under the pyrimidine moiety of the adjacent... 

Nucleoside phosphorylases that catalyse the reversible cleavage of purine nucleosides to the free bases and ribose-1-phosphate are found in most cells, although a phosphorylase that will cleave adenosine has so far been identified only in bacteria. Recent studies have shown that ribo- and 2 -deoxyribofurano-syltransferase activity is associated with phosphorylase activity [19, 23., 222] and that both activities reside in one enzyme, which can be converted from one form to the other by substrate or product binding [20]. Upon crystallization of the enzyme from human erythrocytes a marked decrease in the ribosyl transfer reaction was observed [21b]. 

A one-pot procedure for the transformation of 6-thiopurine nucleosides to 6-aminopurines was developed using DMDO as the oxidant in the presence of a stoichiometric amount of various amines <1996T6759>. For example, 6-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)purine was readily converted to the 6-alkylamino derivatives (6-amino, 75% yield 6-methylamino, 55% yield). Similarly, A -6-acetyl-8-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine was converted to A -6-acetyl-8-methylamino-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine (DMDO, methylamine, CH2CI2, 25 °C, 83% yield). Less nucleophilic 2-mercaptopurine derivatives did not undergo the displacement reaction, however, and only the products of dithiane formation and desulfurization were isolated. 

An example which supports the trans rule is the condensation of 2,5-di-0-benzoyl-3-deoxy-3-phthalimido-/3-D-ribosyl chloride, a glycosyl halide containing the Cl-C2-trans structure, with mercuri derivatives of certain purines only nucleosides of the /3-d type are obtained.202 227... 

The crystal structure of 8-bromoinosine [BRINOSIOI with two molecules A, B in the asymmetric unit (Fig. 17.60) contains a centrosymmetric base-pair configuration. It has an interesting overall pseudosymmetry, linking the functional ribosyl groups of one molecule to the purine of the other. 

It has been shown that the accumulation of 5-amino-iV-D-ribosyl-4-imidazolecarboxamide in a purine-requiring mutant of Escherichia coli ceases when the bacteria are supplied with an excess of purine. The site of inhibition is, apparently, before the formation of the imidazole ring occurs, but after the formation of the D-ribosyl moiety, since adenine has only a... 

It is reported that a purine-requiring mutant of Escherichia coli accumulated a substance related to 5-amino-iV-D-ribosyl-4-imidazolecarboxamide. Its ultraviolet absorption spectrum and its diazo chromogen spectrum differed from those of the known D-ribosyl derivative. Escherichia coli (strain B-96) converts it to 5-amino-4-imidazolecarboxamide, and it can be utilized by Escherichia coli B. It was suggested that it is an amino-(D-ribosyl)-imidazole. The accumulation of this substance was, however, somewhat surprising, since bacterial extracts of the purine-requiring mutant effected synthesis of 5-amino-4-imidazolecarboxamide from o-ribose 5-phosphate together with adenosine 5-triphosphoric acid and an energy source. 

Escherichia coli B was incubated with 2,6-diaminopurine (XXIV), and 6-amino-2-(methylamino)-9-(5-0-phospho-D-ribosyl)purine (XXV) was isolated from the acid-soluble extract of the cells. 5-Nucleotidase liberated a nucleoside containing D-ribose. Hydrolysis of the nucleoside (or nucleotide) with N hydrochloric acid liberated 6-amino-2-(methylamino)purine, which was identified by paper chromatography and by its ultraviolet absorption spectrum. The chromatographic and ion-exchange behavior of the extract also suggested the presence of either a pyrophosphate or a triphosphate of the 6-amino-2-methylamino-(D-ribosyl)purine. In a similar manner, 2,6-diamino-9-(5-0-phospho-D-ribosyl)purine (XXVI) was isolated and identified, together with its possible pyrophosphate or triphosphate. 2,6-... 

Extracts of certain bacteria requiring 2-deoxyribonucleosides, namely, Lactobacillus helveticus, Lactobacillus delbriickii, and Thermobacterium acidophilus R 26, catalyze the transfer of the 2-deoxy-D-ribosyl group from one purine or pyrimidine to another. " 2-Deoxyribosyl -uracil, thy-... 

Phosphorolysis of ribosylpurines, 2-deoxy-D-ribosyl -purines, uridine, and thymidine has been detected in a number of bacteria. ... 

Poly(ADP-ribose) polymerase (PADPRP) hypothesis. - In this theory DNA is the initial target of the mustard agent. Alkylated DNA purines undergo spontaneous and enzymatic depurination, leading to the production of apurinic sites which are cleaved by apurinic endonucleases to yield DNA breaks. Accumulation of DNA breaks leads to activation of the chromosomal enzyme PADPRP, which utilizes nicotinamide adenine dinucleotide (NAD ) as a substrate to ADP-ribosylate and a variety of nuclear... 

SYNS 6-MERCAPTOPURINE RIBOSIDE NSC-4911 RIBOFURANOSIDE, 9H-PURINE-6-THIOL-9 RIBOSYL-6-THIOPURINE THIONOSINE 6-THIOPURINE RIBONUCLEOSIDE 6-THIOPURINE RIBOSIDE TIOINOSINE... 

SYNS 6-METHYLMERCAPTOPURINE RIBONUCLEO-SIDE 6-METHYLMERCAPTOPURINE RIBOSIDE 6-METHYL-9-RIBOFURANOSYLPURINE-6-THIOL 6-METHYL-MP-RIBOSIDE 6-METHYLTHIOINOSINE 6-(METHYLTHIO)PURINE RJBONUCLEOSIDE 6-METHYLTHIOPURINE RIBOSIDE NCI-C04784 NSC-40774 P-d-RIBOSYL-6-METHYLTHIOPURINE SQ 21977... 

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