Adenine nucleosides, precursors

Except for silylated pyrimidine and purine bases, silylated imidazoles and tri-methylsilylazide undergo similar glycosidation in the presence of la, leading to a variety of nucleoside precursors or analogs [74]. As first reported by Isono, la and 6a are also effective Lewis acids in the transglycosidation of pyrimidine 65 to afford adenine nucleoside 67 (Sch. 44) [75]. 

Further work on griseolic acid analogues has been reported (see Vol. 25, p. 232), giving guanosine analogues, e.g. 28, instead of adenine derivatives and its 3, 4 -stereoisomers together with carbocyclic analogues. Other carbocyclic nucleoside derivatives of aristeromycin and a synthesis of carbovir are mentioned in Chapter 20, and a synthesis of the carbocyclic nucleoside precursor, Ohno s lactone, is referred to in Cluster 18. 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

B. The first nucleotide to be added must base-pair with adenine. However, DNA polymerase cannot initiate synthesis of strands. RNA polymerase (the primase) produces a short primer that DNA polymerase can extend. Therefore, the first nucleoside must be a ribonucleotide that base-pairs with adenine, that is, UTP. (Nucleoside triphosphates serve as precursors for the polymerases.)... 

Purine nucleosides, with the exception of adenosine, are salvaged by converting them into the base followed by phosphoribosylation. Adenosine is phosphorylated directly by adenosine kinase or deaminated by adenosine deaminase to inosine. Adenine and adenosine deaminase are present in the sporozoite and merozoite forms (64) the former is not in extracts from unsporulated oocysts (11) but the latter has apparently not been looked for. The ability to deaminate both adenine and adenosine allows this parasite to synthesize guanine nucleotides in the absence of AMP deaminase. The ratio of labeled adenine nucleotides to guanine nucleotides is about 20% higher when both adenine and adenosine are the precursors compared to the ratio obtained when hypoxanthine or inosine was used (64). This indicates that although the major route of salvage for adenine and adenosine is by conversion into hypoxanthine, there is some direct conversion of these compounds into AMP. 

To date there is no report about the biosynthesis of aromatic cytokinins. In view of the dissimilarity between the aromatic and the isoprenoid(-derived) A side chains it is likely that their biosynthetic pathways are quite different. Phenylalanine may be considered as a starting compound and benzaldehyde and/or hydroxylated benzaldehydes as immediate side chain precursors. However, the existence of some crossing-points between aromatic and isoprenoid side chain formation cannot be completely excluded. There is also the possibility that the enzymes of adenine and/or purine metabolism, which are not strictly specific, may catalyse some mutual conversions among BA-bases, nucleosides and nucleotides [81]. 

The nucleoside monophosphates are converted to the triphosphates (the direct precursors of RNA) by two kinase reactions These kinases have a low specificity, and they catalyse the phosphorylation of nucleotides of adenine, guanine and the pyrimidines (Fig. 3). An alternative route for the synthesis of purine nucleotides is the Salvage pathway (see). 

Amino-4-imidazole carboxamide ribotide, a precursor only two steps removed (formylation and cycli-zation) from inosinic acid, can be synthesized by the direct condensation of the imidazole with 5-phosphori-bosyl pyrophosphate. The enzyme catalyzing this reaction was purified from an acetone powder of beef liver. The same enzyme (AMP pyrophosphorylase) catalyzes the condensation of adenine, guanine, and hypoxan-thine. Nucleoside phosphorylase is an enzyme that catalyzes the formation of a ribose nucleoside from a purine base and ribose-1-phosphate. Guanine, adenine, xanthine, hypoxanthine, 2,6-diaminopurine, and aminoimidazole carboxamide are known to be converted to their respective nucleosides by such a mechanism. In the presence of a specific kinase and ATP, the nucleoside is then phosphorylated to the corresponding nucleotide. 

Uric Add Formation. In vertebrates purines are oxidized to uric acid. This reaction is catalyzed by xanthine oxidase (or dehydrogenase), which attacks both hypoxanthine and xanthine.Since adenine and guanine nucleotides can give rise to the hydroxylated purines either as the nucleotide, nucleoside, or free base, all of the naturally occurring purines of animals can be converted to uric acid. Adenine may also be oxidized to 2,8-dihydroxy-4-aminopurine, which is excreted in the urine. The formation of uric acid from any of its precursors is followed conveniently spectrophotometrically (Fig. 29). ... 

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