2 -DEOXYRIBONUCLEOSIDES

The Pd-mediated coupling involving organomercury and alkenes is useful for the synthesis of C-5 substituted 2 -deoxyribonucleosides[376]. The ethylur-idine 415 is prepared by the reaction of the 5-chloromercuriuridine 414 with... 

FIGURE 28 9 The new polynucleotide chain grows by reaction of its free 3 OH group with the 5 triphosphate of an appropriate 2 deoxyribonucleoside... 

Inspired by its natural function, RibA has been applied in a multienzymatic commercial process for the production of different purine or pyrimidine containing deoxyribonucleosides such as (115) in good yield (Figure 10.42) [184,185]. 

Prusoff WH, Chen MS, Fischer PH, Lin TS, Shiau GT, Schinazi RF, Walker J (1979) Antiviral iodinated pyrimidine deoxyribonucleosides 5-iodo-2 -deoxyuridine 5-iodo-2 -deoxycytidine 5-iodo-5 -amino-2, 5 -dideoxyuridine, Pharmacol Ther 7 1-34... 

The reduction of ribonucleoside triphosphates by various dithiols which are capable of intramolecular cyclization on oxidation (dihydrolipoate, dithioerythritol, dithiothreitol) yields 2 -deoxyribonucleoside triphosphates. These reactions also require 5-deoxyadenosylcorrinoids. 

Conversion of purines, their ribonucleosides, and their deoxyribonucleosides to mononucleotides involves so-called salvage reactions that require far less energy than de novo synthesis. The more important mechanism involves phosphoribosylation by PRPP (structure II, Figure 34-2) of a free purine (Pu) to form a purine 5 -mononucleotide (Pu-RP). 

REDUCTION OF RIBONUCLEOSIDE DIPHOSPHATES FORMS DEOXYRIBONUCLEOSIDE DIPHOSPHATES... 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Figure 34-5. Reduction of ribonucleoside diphosphates to 2 -deoxyribonucleoside diphosphates.

Figure 34-8. Formation of uric acid from purine nucleosides byway of the purine bases hypoxanthine, xanthine, and guanine. Purine deoxyribonucleosides are degraded by the same catabolic pathwayand enzymes,all of which existin the mucosa of the mammalian gastrointestinal tract.

Figure 36-14. The initiation of DNA synthesis upon a primer of RNA and the subsequent attachment of the second deoxyribonucleoside triphosphate.

During the S phase, mammahan cells contain greater quantities of DNA polymerase than during the nonsynthetic phases of the cell cycle. Furthermore, those eiKymes responsible for formation of the substrates for DNA synthesis—ie, deoxyribonucleoside triphosphates—are also increased in activity, and their activity will diminish following the synthetic phase until the reappearance of the signal for renewed DNA... 

Wondrack LM, C-A Hsu, MT Abbott (1978) Thymine-7-hydroxylase and pyrimidine deoxyribonucleoside 2 -hydroxylase activities m Rhodotorula glutinis. J Biol Chem 253 6511-6515. 

Wetzstein H-G, N Schmeer, W Karl (1997) Degradation of the fluoroquinolone enrofloxacin by the brown-rot fungus Gleophyllum striatum identification of metabolites. Appl Environ Microbiol 63 4272-4281. Wondrack LM, C-A Hsu, MT Abbott (1978) Thymine-7-hydroxylase and pyrimidine deoxyribonucleoside 2 -hydroxylase activities in Rhodotorula glutinis. J Biol Chem 253 6511-6515. 

Berger, M., Anselmino, C., Mouret, J.F. and Cadet, J. (1990). H performance liquid chromatography-electrochemical assay for monitoring the formation of 8-oxo-7,8-dihydro-adenine and its related 2 -deoxyribonucleoside. J. Liquid Chromatog. 13, 929-940. 

Figure 8.24 Separation of the major deoxyribonucleosides and their 5 - monophosphate deoxynucleotides on a strong cation exchange column (column one) and a reversed-phase column. The unseparated nucleosides. A, on the ion- exchange column were switched to the reversed-ptose column. Pe2dc Identification A = nucleosides, B d-CMP, C d-AMP, D - d-GJIP, E - d-CVD, P d-UKO, G THD, and H = d-AOO. (Reproduced with permission from ref. 298. Copyright Preston Publications, Inc.)...

Stack, D. E. Byun, J. Gross, M. L. Rogan, E. G. Cavalieri, E. L. Molecular characteristics of catechol estrogen quinones in reactions with deoxyribonucleosides. Chem. Res. Toxicol. 1996, 9, 851-859. 

Breter, H.-J., Seibert, G., and Zahn, R. K., Single-step separation of major and rare ribonucleosides and deoxyribonucleosides by high-performance liquid cation-exchange chromatography for the determination of the purity of nucleic acid preparations, ]. Chromatogr., 140, 251, 1977. 

Polystyrene-supported deoxyribonucleoside-3 phosphoramidites (160), or analogous compounds bound to the support via a piperazine... 

In the approach using bis(tetrazolyl)morpholinophosphine for synthesizing bis (deoxyribonucleoside) phosphates it is not necessary to protect the 3 -hydroxyl group of die second deoxyribonucleoside (selective attack on the 5 -OH).[983,[1003 In this reaction bis(tetrazolyl)morpholinophosphine is superior to other bis(azolyl)moipholinophosphines or azolylchloromorpholinophosphines.11 13... 

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