Ribonucleoside derivatives

The groups of Hirao and Yokoyama have examined various new base pairs. Base-pairing partners for 6-thienylpurine nucleoside (114) have been examined. This does not form stable base pairs with thymidine as there is a steric clash between the thienyl group and the thymidine C4-oxo group, but specific base pairs are obtained with the pyridinone analogues (115). The 5 -triphosphates of the ribonucleoside derivatives (115) were incorporated specifically opposite (114) with T7 RNA polymerase. In addition, (115, R=phenylethynyl) was shown to stabilise an internal loop of a theophylline-binding RNA aptamer. " Pyrrole-2-carbaldehyde derivatives (116) also form specific base pairs with the... 

Another elimination process that transforms 1,2-diol dimesylates (e.g., ribonucleoside derivatives) to alkenes uses NaBH4 in conjunction with catalytic quantity of bis(4-perflu-orohexylpheny) di.selenide. The diselenide is readily recovered. 

Pitsch S, Weiss P, Luzzi J. Ribonucleoside derivative and methods for preparing the same. Swiss Patent Application 01 937/97, August 18, 1997. 

A2-Isobutryl-7-(2 -deoxy-P-D-erthyro-pentofuranosyl)guanine (140) has been synthe.sised from the corresponding ribonucleoside derivative in a 4-step deoxygenation procedure. Following suitable derivatisation for synthesis this was incorporated into oligonucleotides. A suitable... 

Since the report in 1986 that 3 -azido-3 -deoxythymidine (AZT, now called zidovudine) (152) was effective against human retroviruses <86GEP(O)3608606>, a plethora of ribonucleoside derivatives have been prepared and their pharmaceutical properties studied and reported. Only a few representative examples (152)-(164) are discussed here space limitations do not allow for a comprehensive overview. 

Kawashima E, Aoyama Y, Sekine T, et al. Sonochemical and triethylborane-induced tin deuteride reduction for the highly diastereoselective synthesis of (2 R)-2 -deoxy [2 - H]ribonucleoside derivatives. J Org Chem. 1995 60 6980-6986. 

Bridson PK, Jiricny J, Kemal 0, Reese CB (1980) Reactions between ribonucleoside derivatives and formaldehyde in ethanol solution. J Chem Soc Chem Commun 208-209... 

Pyrimidine ribonucleotides, like those of purines, may be synthesized de novo from amino acids and other small molecules (Chapter 11). Preformed pyrimidine bases and their ribonucleoside derivatives, derived from the diet of animals or found in the environment of cells, may be converted to ribonucleotides via nucleoside phosphorylases and nucleoside kinases. In some cells a more direct pyrimidine phosphoribosyltransferase pathway has also been recognized (Chapter 12). Ribonucleotides are catabolized by dephosphorylation, deamination, and cleavage of the glycosidic bond, to uracil. Uracil may be either oxidatively or reductively cleaved, depending on the organism involved, and can be converted to CO and NH (Chapter 13). 

When cytidine was the sole pyrimidine source (Table 14r-II), polynucleotide cytidylate and deoxycytidylate had identical specific activities and were incorporated without dilution. This is convincing evidence that in E. colt, reduction of ribonucleoside derivatives is able to supply all of the deoxyribose for DNA components without appreciable contribution from other sources, such as the postulated sequence involving deoxyri-boaldolase mentioned above. It will be recognized that this result does not preclude the possibility that alternate routes of deoxyribosyl biosynthesis may operate in circumstances other than the special ones of the Karlstrdm and Larsson experiment. The details of ribonucleotide reduction are discussed at length in Chapter 16. 

The concept that the deoxyribosyl groups of DNA nucleotides are derived by reduction of ribonucleoside derivatives is based on a wide array of experimental evidence. 

The ribonucleoside derivative of AIR, 5-aminounidazole ribonucleoside, has been isolated from culture filtrates of a purine-requiring mutant of E. coli (124). It was probable that the ribonucleotide was formed first within the bacterial cell, dephosphorylated, and released into the medium. The free base, 5-aminoimidazole, was a product of purine catabolism by microorganisms (114). 

In support of its role as an intermediate in purine metabolism, adenylosuccinic acid has been isolated from mammalian liver (164) and from Penidllium chrysogenum (166). The free base, adeninosuccinic acid [6-(succinoamino) purine], was identified in human urine (166) and isolated from Neurospora mutants (167, 168). Also, the ribonucleoside derivative of adeninosuccinic acid (adeno lsuccinic acid) has been found in human cerebrospinal fluid (169) and in a Neurospora mutant (168). Another adenylosuccinate compound contained sulfate in a ribos fi -phosphosulfate linkage as well as a peptide residue, but its significance is not known (160). 

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