Inosine 2-deoxy

Inosine, 6-benzyloxy-9- -D-ribofuranosyl-2-dimethylamino-hydrogenolysis, 5, 558 Inosine, 2 -deoxy-alkylation, 5, 538 Inosine, 6-phenacylthio-dethiation, S, 559 Inosine 5 -monophosphate biosynthesis, 1, 88 Inosines, thio-synthesis, 5, 584 Inositol, D-l,4-anhydro-synthesis, 1, 416 Inositols synthesis, 1, 416 Insecticides... 

By analogy with the conversion of uridine 1 into cytidines 6, the conventional amination of inosine 235a, guanosine 235b, or xanthosine 235c and their 2 -deoxy analogues to the adenosines 237 requires ... 

The susceptibilities of some of these fluorinated purine nucleosides to the action of enzymes are now described. In contrast to the inertness of the 2 -deoxy-2 -fluoro- and 3 -deoxy-3 -fluorocytidine analogs 739, 744, and 821 towards cytidine deaminase, the adenosine compounds 867, 883, and 906 are readily deaminated - by the adenosine deaminase in erythrocytes and calf intestine, but the resulting (deaminated) inosine compounds (from 867 and 883), as well as 888, are highly resistant - to cleavage by purine nucleoside phosphorylase (to give hypoxanthine base for the first two). The reason was discussed. Both 867 and 883 can form the 5 -triphosphates, without deamination, in human erythrocytes or murine sarcoma cells in the presence of 2 -deoxycoformycin, an adenosine deaminase inhibitor, but... 

A nucleoside consists of a purine or pyrimidine base linked to a pentose, either D-ribose to form a ribonucleo-side or 2-deoxy-D-ribose to form a deoxyribonucleoside. Three major purine bases and their corresponding ribo-nucleosides are adenine/adenosine, guanine/guanosine and hypoxanthine/inosine. The three major pyrimidines and their corresponding ribonucleosides are cytosine/ cytodine, uracil/uradine and thymine/thymidine. A nucleotide such as ATP (Fig. 17-1) is a phosphate or polyphosphate ester of a nucleoside. 

Fig. 14.1 Cellular pathway of methotrexate. ABCBl, ABCCl-4, ABC transporters ADA, adenosine deaminase ADP, adenosine diphosphate AICAR, aminoimidazole carboxamide ribonucleotide AMP, adenosine monophosphate ATIC, AICAR transformylase ATP, adenosine triphosphate SjlO-CH -THF, 5,10-methylene tetrahydrofolate 5-CHj-THF, 5-methyl tetrahydro-folate DHFR, dihydrofolate reductase dTMP, deoxythymidine monophosphate dUMP, deoxy-uridine monophosphate FAICAR, 10-formyl AICAR FH, dihydrofolate FPGS, folylpolyglutamyl synthase GGH, y-glutamyl hydrolase IMP, inosine monophosphate MTHFR, methylene tetrahydrofolate reductase MTR, methyl tetrahydrofolate reductase MTX-PG, methotrexate polyglutamate RFCl, reduced folate carrier 1 TYMS, thymidylate synthase. Italicized genes have been targets of pharmacogenetic analyses in studies published so far. (Reproduced from ref. 73 by permission of John Wiley and Sons Inc.)...

With over-expressed fluorinase and under optimised reaction conditions, a synthesis of [ F]-FDA 5d from [ F]-fluoride was achieved in a radiochemical yield (RCY) of 95%. Also in coupled enzyme systems, where the fluorinase is coincubated with other enzymes, the syntheses of [ F]-5 -fluoro-5 -deoxy-inosine... 

Kakiuchi, N., Marck, C., Rousseau, N., Leng, M., De Clerq, E. and Guschlbauer, W. (1982) Polynucleotide helix geometry and stability. Spectroscopic, antigenic and interferon-inducing properties of deoxyribose-, ribose-, or 2 -deoxy-2 -fluororibose-containing duplexes of poly(inosinic acid), poly(cytidylic acid). J. Biol. Chem., 257, 1924-1928. 

Synthesis of 6-Chloropurine 3 -deoxy riboside We first investigated the practical synthesis of 6-chloropurine-3 -deoxyriboside starting with inosine, which was readily available in suitable quantities (see Scheme 7.16). 

Remaining issues. We developed a new route to the practical synthesis of FddA from inosine in nine steps and 36% overall yield. During the course of this study, we greatly improved the fluorination of 3 -deoxyriboside, which had been very difficult and the bottleneck in FddA synthesis. However, even with this process, formation of the elimination byproduct was inevitable. To further improve the yield, studies are still needed to fix the 3 -deoxy riboside to the 2 -endo conformation, which does not easily give the elimination product. 

Purine nucleosides are cleaved by the action of purine nucleoside phosphorylase with the liberation of ribose 1-phosphate (Kl, PI). The enzyme is apparently specific for purines. The material from erythrocytes catalyzes the phosphorolysis of purine but not pyrimidine nucleosides (T6.) Purine phosphorylase activity is found widespread in nature and in many animal tissues (FIO). Friedkin and Kalckar investigated an enzyme capable of cleaving purine deoxynucleosides to the aglycone and deoxy-ribose 1-phosphate. They concluded that the enzyme was identical to that which splits purine ribonucleosides (F8, F9). This enzyme is capable of degrading inosine, xanthosine, and guanosine to forms readily attacked by other enzymes. In so doing, it permits living cells to retain the ribose and deoxyribose moieties. 

Figure 3.14 Structures of common nucleosides whose acid-catalysed hydrolysis has been studied. Adenosine, guanosine and cytidine are three of the four common nucleosides in RNA and their 2 -deoxy derivatives in DNA, whereas uridine is found only in RNA and 2 -deox5hh5midine in DNA. Psicofuranine is an antibiotic and is not a common constituent of nucleic acids. Inosine is a commonly used substrate in investigations of enzymic ribosyl transfer.

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