9-Methyl hypoxanthine, reaction with

Another C-alkylation of purines is the free-radical reaction with alkyl hydroperoxides catalyzed by iron(II) ions. This reaction has been applied to guanine, hypoxanthine, and adenine, as well as their nucleosides. A typical example is the 8-methylation of guanine to give 5 other examples are listed in Table 42. 

Thiation of purine, 6-methyl- or 2-amino-purines with hot sulfur leads to the 8-thioxo derivatives (64JOC3209). The reaction failed with guanine, hypoxanthine and 6-chloropurine but was successful with 1,9-dimethyl-, 7,9-dibenzyl- and 7,9-dimethyl-hypoxanthines... 

The reaction fails when the purine contains electron-donating substituents. Thus, 2-(methyl-sulfanyl)adenine does not hydrolyze to any significant extent in 6 M hydrochloric acid. On the other hand, 2-(methylsulfanyl)hypoxanthine is readily converted into xanthine (4) by acid hydrolysis. S -Carboxymethylpurines which arc conveniently prepared from sulfanylpurines in aqueous alkaline solution with chloroacetic acid are used as intermediates in the conversion of sulfanylpurines into hydroxypurines, c.g. the conversions 2 - 3 4, and 5- 6- 1. ... 

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

Hypoxanthine is oxidized at carbon 2 by both molybdenum hydroxylases, although xanthine oxidase is much more effective as a catalyst in this reaction [ 10]. A methyl substituent in this position prevents oxidation by either enzyme. Introduction of A-methyl substituents into the hypoxanthine nucleus produces dramatic effects on enzymic oxidation rates and also gives some insight into the productive modes of binding to each enzyme. Thus, it has been proposed that hypoxanthine tautomerizes in the xanthine oxidase-substrate complex to the 3-NH-form with a simultaneous shift of the NH-group in the imidazole ring from position 9 to 7 [ 198,200]. In support of this hypothesis, when tautomerism in the imidazole ring is prevented by substitution at N-7 or N-9, such compounds are almost refractory to oxidation (see Table 3.9)... 

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