Adenine methyl derivatives

The action of methyl toluene- -sulfonate on adenine (113 R = H) is reported to give the 3-methyl derivative (114), while the action... 

PES has been applied to study biologically active molecules with amino groups and their constituents like nucleic bases and related compounds (e.g. adenine, guanine, thymine, cytosine, hypoxanthine and their methyl derivatives)113-120 and amino acids92,121,122 or their methyl esters123. 

The presence of the cation protonated on N-1 cannot account for the fluorescence of aqueous acidic adenine solutions (pH = 2), since the 1-methyl derivative does not fluoresce under the same conditions (Borresen, 1967). It has therefore been suggested that other tautomeric forms of the cation are also present, the fluorescent tautomer probably being protonated on the amino-group with another proton on N-7. Quantum mechanical calculations (Veillard and Pullman, 1963) indicate similar proton affinity for N-1 and N-3, and a lesser one for N-7. There are numerous calculations in the literature on the electronic structure of adenine (see Boyd, 1972, and references quoted therein) and a recent one on N-7-H and N-9-H tautomers protonated on N-1 (Jordan and Sostman, 1972). The N-9-H form is preferred according to hoth MINDO and CNDO/2 calculations. 

The bases that occur in nucleic acids are aromatic heterocyclic compounds derived from either pyrimidine or purine. Five of these bases are the main components of nucleic acids in all living creatures. The purine bases adenine (abbreviation Ade, not A ) and guanine (Gua) and the pyrimidine base cytosine (Cyt) are present in both RNA and DNA. In contrast, uracil (Ura) is only found in RNA. In DNA, uracil is replaced by thymine (Thy), the 5-methyl derivative of uracil. 5-methylcyto-sine also occurs in small amounts in the DNA of the higher animals. A large number of other modified bases occur in tRNA (see p. 82) and in other types of RNA. 

The tRNA molecules have single chains with between 73-93 ribonucleotides. Most of the tRNA bases are adenine (A), cytosine (C), guanine (G), and uracil (U). There also are a number of unusual bases that are methylated derivatives of A, C, G, and U. 

Dias RMB, Vieira AJSC (1997) Substituent effect on superoxide elimination from peroxyl radicals of adenine and methylated derivatives. J Photochem Photobiol AChem 117 217-222 Didenko YT, Nastish DN, Pugach SP, Polovinka YA, Kvochka VI (1994) The effect of bulk solution temperature on the intensity and spectra of water sonoluminescence. Ultrasonics 32 71-76 Dillon D, Combes R, McConville M, Zeiger E (1992) Ozone is mutagenic in Salmonella. Environ Mol Mutagen 19 331-337... 

Jurecka, R Hobza, P. True stabilization energies for the optimal planar hydrogen-bonded and stacked stmctures of guanine "cytosine, adenine-"thymine, and their 9- and 1-methyl derivatives complete basis set calculations at the MP2 and CCSD(T) levels and comparison with experiment, J. Am. Chem. Soc. 2003, 125, 15608-15613. 

The naturally occurring purines fall into 4 main groups. (1) Simple substituted derivatives of purine (1) such as adenine (2) and various 6-AT-substituted derivatives. (2) Monoxo-dihydropurines such as hypoxanthine (3), guanine (4), and isoguanine (5). f3) Dioxotetra-hydropurines such as xanthine (6) and methylated derivatives including the 3,7-dimethyl derivative theobromine (7), 1,3-dimethylxanthine or theophylline f8), and 1,3,7-trimethylxanthine or caffeine (9). (4) Trioxohexahydropurines such as uric acid (10). 

Comparison of the photoelectron spectra of purine, adenine and their 7- and 9-methyl derivatives in the gas phase revealed that the spectra of purine and adenine are both much more like the spectra of their 9-methyl rather than their 7-methyl derivatives. This suggests that in an isolated environment the N(9)H tautomers of both purine and adenine are more stable than the N(7)// forms. 

Methylation of adenine 1-oxide produces the 9-methyl 1-oxide (157) via an intermediate O-methyl derivative (Scheme 24) <71CPB161l). 

Free radical alkylation procedures have proved a useful route to alkylpurines which are not readily available by other methods. Thus 6-substituted purines including adenine and hypoxanthine may be converted into 8-methyl derivatives with t-butyl hydroperoxide in the presence of iron(II) ions and acid (74T2677), although small amounts of 2-methyl and 2,8-dimethyl derivatives were formed simultaneously. Adenosine and guanosine similarly furnished the corresponding 8-methyl derivatives with diacetyl peroxide (as a source of methyl radicals) and iron(II) ions (76T337). 

A protonation study of purine and its N -methyl and N -methyl derivatives revealed that purine itself is protonated exclusively at position N-1, whereas N -H, N -H and N -H, N -H tautomers coexist in solution. The dependence of the C chemical shifts of purine, adenine, and adenosine on pH showed that protonation in an HCIO4-containing solution leads to the singly protonated species BH C1()4. whereas solutions containing HCl, TEA, and HSO3F gave mixtures of singly, doubly, and triply protonated species, respectively. ... 

Methylation of purines (and related systems) bearing NH, OH, or SH groups with AW-dimethylformamide dimethylacetal gives the corresponding N-, 0-, and 5-methyl derivatives. With purine itself, 45% of the 7-methyl- and 30% of the 9-methyl-derivative is formed. Alkylation of un-ionized adenine results mainly in alkylation at N-3, whereas alkylation of the anion yields predominantly A -9-substituted adenineMethylation of adenine under phase-transfer conditions gives a nearly quantitative yield of 9-methyladenine. Alkylation of A(-substituted adenines occurs preferentially at N-1, but acylation of the amino-group causes alkylation to occur at N-7. ... 

The NMR results show that, in the case of 3 and 5 nucleotides, the binding of metal, or at least copper, does occur at Nj for adenine and guanine and at Ni for cytosine very little binding of copper occurs in thymine, the methyl derivative of uracil. NMR studies have also shown us that in the polymeric nucleic acids binding occurs generally in the same position as in these monomers. For example, in polyadenylic acid, the binding is also at Nj, and in polycytidylic acid it is at Ni. 

Some examples will be given from the pteridine 2.32) series (all in water at 20°). 4-Aminopteridine is soluble only 1 in 1400, but 4-dimethylaminopteridine 1 in 2 (Albert, Brown and Cheeseman, 1952b). Similarly, 7-hydroxypteridine is soluble only 1 in 900, but both its 0- and iV-methyl-derivatives are soluble 1 in 50. Again, 6-aminopurine 4.3) (adenine) is only soluble 1 in 1100 but 6-dimethylaminopurine 1 in 120 (Albert and Brown, 1954). 

Kinetic studies have shown that the substituent at position 1 and pH also play an important role in the Dimroth rearrangement of adenine and adenosine derivatives. For adenine derivatives substituted at position 1, the individual rates for methyl, ethyl and propyl derivatives were comparable, while the benzyl derivative rearranged faster (not shown). Above pH 10, methyl-substituted adenine derivatives rearranged fastest, while the benzyl-substituted derivatives rearranged the slowest. Subsequently, the authors found that adenosine 130 rearranged faster at pH values below 10, whereas adenoside 128 rearranged faster at pH values above 10, and in both cases the reaction rates were enhanced by the presence of ribose. The authors attributed these observations to the electronic effects of the substituents, which play a greater role at pH values less than 10 where the nucleoside remains protonated. At pH values above pH 10, the adenine/adenosine derivatives are neutral and sterics plays a more important role. 

For many years the urine has been known to contain a number of purine bases in addition to uric acid adenine, guanine, hypoxanthine, xanthine, and several methylated derivatives of the purine bases (N,2-meth-ylguanine, 1-methylguanine, 7-methylguanine, 7-methyl-8-hydroxyguanine, and 1 -methylhypoxan-... 

Several methylated derivatives of purines have been isolated from biological systems. Methyl derivatives of adenine (2-methyl-6-aminopurine or 2-methyladenine 6-dimethylaminopurine or W -dimethyladenine) were... 

Identification of the component pentose sugar confirms whether the polynucleotide chain is RNA or DNA. Both RNA and DNA contain the same two purine bases, adenine (A) and guanine (G) whereas they differ in their content of the pyrimidine bases. RNA contains cytosine (C) and uracil (U) but DNA contains cytosine and the 5-methyl derivative of uracil called thymine (T). In addition to these bases, called major bases, DNA and RNA also contain altered or less common bases called minor bases. In DNA, the minor bases are usually methylated derivatives of the major bases which play a special role in the functioning of the polynucleotide. RNAs, especially transfer RNAs, also contain minor bases, e.g. inosine, pseudouridine (in which uracil is linked through C-5, not N-1, to ribose), dihydrouridine, ribosylthymine and methylated derivatives of nucleosides (Figure 7.2). Minor bases are mainly modified versions of major bases. 

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