Purines hydroxylation

These relationships are general Hydroxyl substituted purines and pyrimidines exist in their keto forms ammo substituted ones retain structures with an ammo group on the ring The pyrimidine and punne bases m DNA and RNA listed m Table 28 1 follow this general rule Beginning m Section 28 7 we 11 see how critical it is that we know the cor rect tautomeric forms of the nucleic acid bases... 

Acetylation of hydroxyl groups and esterification of carboxyl groups have been observed ia a limited number of cases but, ia geaeral, have ao preparative advantage over chemical methods. By comparison, phosphorylation has been useful ia the preparatioa of modified purine and pyrimidine mononucleotides from their corresponding nucleosides, eg, 6-thioguanosiae [85-31-4] (51) (97). 

There has been considerable interest recently in the quatemization of purine compounds, although most of those examined have contained hydroxyl or amino substituents and therefore products may be regarded as the acid salts of N-alkylated derivatives. 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

All these steps proceed to afford free or N -substituted crystalline cytidines 6 in high yields [11] (cf. the preparation of N (tetramethylene)cytidine 6b in 95.4% yield in Section 1.1.). This simple one-pot reaction is also very easy to perform on a technical scale, as are the subsequently discussed analogous silylation-aminations of purine nucleosides and other hydroxy-N-heterocycles (cf. Sections 4.2.4 and 4.2.5). The concept of silylation-activation while simultaneously protecting hydroxyl groups in alcohols, phenols, or phosphoric acids by silylation was subsequently rediscovered and appropriately termed transient protection [16-18]. 

Although pyridines and quinolines were first produced during the carbonization of coal, they are now available by synthesis in quantities that far exceed those by the former. Phosphorylated ribosides of hydroxylated and aminated pyrimidines and purines make up the basic structure of ribonucleic and deoxyribonucleic acids. The polycyclic oxaarenes are plant metabolites, while thiaarenes are primarily important components of high-sulfur petroleum that must be removed. 

Although it had been assumed that only hypoxanthine dehydrogenase is required for the conversion of hypoxanthine (6-hydroxypurine) into uric acid, in Clostridium purinolyti-cum, two enzymes, both of which contain a selenium cofactor, are required. The enzymes differ in the molecular mass of their subunits, in their terminal amino acid sequences, in their kinetic parameters, and in their specific activities for purines (Self and Stadman 2000). Purine hydroxylase converts purine into hypoxanthine and xanthine (2,6-dihy-droxypurine), which is then further hydroxylated to uric acid (2,6,8-trihydroxypurine) by xanthine dehydrogenase (Self 2002). 

A variety of methods for modified oligonucleotide preparations have been reported including (1) the C5 and C4 positions for the pyramidines, (2) the exocyclic amino groups and the C8 positions of the purines, and (3) the 2 -hydroxyl group of the carbohydrate residue. Every method should be important as the basis for new immobilization chemistry, however, we especially focused our attention on the use of oligodeoxyribonucleotide phos-phorothioates (Fig. 3). 

Interestingly, the nucleophilic addition of water in the sequence of events giving rise to 41 represents a relevant model system for investigating the mechanism of the generation of DNA-protein cross-links under radical-mediated oxidative conditions [80, 81]. Thus, it was shown that lysine tethered to dGuo via the 5 -hydroxyl group is able to participate in an intramolecular cyclization reaction with the purine base at C-8, subsequent to one electron oxidation [81]. 

Hydroxyl radicals are the most reactive free-radical species known and have the ability to react with a wide number of cellular constituents including amino-acid residues, and purine and pyrimidine bases of DNA, as well as attacking membrane lipids to initiate a free-radical chain reaction known as lipid peroxidation. 

Pyrimido-fused purines can be prepared by intramolecular cyclization of A -(3-hydroxypropyl)guanines, a reaction similar to that of Equation (202). This cyclization can be achieved either via the mesylate <1997JME3248> or (presumably) by conversion of the hydroxyl substituent to chloro (Equation 204) <2001CPB188, 2002JME3440>. 

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