Hydroxypurines

C. Tiglium L. Crotonoside (6-amino-2-hydroxypurine-d-riboside) (Cherbuliez et al., Helv. Chim. Acta., 1932, 15, 464, 978). 

At the present time, the greatest importance of covalent hydration in biology seems to lie in the direction of understanding the action of enzymes. In this connection, the enzyme known as xanthine oxidase has been extensively investigated.This enzyme catalyzes the oxidation of aldehydes to acids, purines to hydroxypurines, and pteridines to hydroxypteridines. The only structural feature which these three substituents have in common is a secondary alcoholic group present in the covalently hydrated forms. Therefore it was logical to conceive of this group as the point of attack by the enzyme. 

The relation between tautomcrism and enzymatic oxidation of various hydroxypurines has been discussed by Bergmann and his associates. ... 

The anaerobe Peptococcus (Micrococcus) aerogenes had a dehydrogenase that carried out specific hydroxylation at the 6-positions of 2- and 8-hydroxypurine, and was therefore distinct from xanthine dehydrogenase from which it could be separated (Woolfolk et al. 1970). It was also able to carry out dismutation of 2-hydroxypurine to xanthine (2,6-dihydroxypurine) and hypoxanthine (6-hydroxypurine). 

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). 

Methylation of some form of 6-mercaptopurine in man has been established by the identification of 6-(methylsulphinyl)-8-hydroxypurine (LXV), 6-(methylthio)uric acid (LX), and 6-(methylthio)-8-hydroxy-A -glucuronide (LXVll). The oxidation of 6-(methylthio)purine to 6-(methylthio)-8-hydroxy-purine (LXVl) is mediated much more rapidly by rabbit liver aldehyde oxidase than by xanthine oxidase, and the oxidation is not inhibited by 4-hydroxy-pyrazolo [3, 4-d] pyrimidine [269], which is known to be an effective inhibitor of xanthine oxidase, and consequently, of the oxidation of 6-mercaptopurine [12,268]. 

An alternative strategy for the synthesis of 9-alkoxypurines is via the coupling of a suitably functionalized 9-hydroxypurine with protected alcohols such as 1014 under the Mitsunobu condition or with halides under base-catalyzed conditions to give after deprotection 998 or its adenosine analog 1015 (90TL2185). 

Levinson et al. (1991) reported that a nitrogenous waste, guanine (2-amino-6-hydroxypurine), functioned as an aggregation pheromone of the flour mite Ac. siro, together with ammonia as a kairomone. However, because guanine is nonvolatile, it should probably be classified as an arrestant rather than an aggregation pheromone. 

Amino-6-hydroxypurine, AEl6 6-Amino-2-hydroxypurine, AE17 2-Am i no-4-hydroxypyr i midi ne, AC67... 

Deoxyinosine is not considered to be a normal constituent of deoxyribonucleic acid. Deaminases are present in deoxyribonucleic acid which convert (see Ref. 69) deoxyadenosine to IX. Earlier methods for isolation of the nucleosides of deoxyribonucleic acid usually yielded the hypoxanthine (6-hydroxypurine) nucleoside instead of deoxyadenosine. 

The lactam-lactim, tautomerism, of hydroxypurines illustrated, for example, for hypoxanthine by the structures 8 and 9. 

For this particular problem the theory drags somewhat behind experimental evidence, at least insofar as the question of the relative stability of the two forms is concerned. The experimental evidence coming mainly from infrared spectroscopy unambiguously shows12 that the three isomeric 2-, 6-, and 8-hydroxypurines (29-31) all exist essentially, both in the solid state and in solution, in the oxo form, as they all present the characteristic C=0 stretching vibration (near 1670 cm 1 in the 2- and 6-hydroxypurines and near 1740 cm-1 in the 8-hydroxy isomer) and show no band which could be attributed... 

If the study of the relative stability of the lactam and lactim forms of hydroxypurines thus escapes a rigorous quantitative treatment, the situation is more agreeable with respect to some other electronic properties of the two forms, which are much less sensitive to the details of the structure and, in particular, to the distance of the... 

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