2- Hydroxypurine

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

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). 

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

If we take as reference the dipole moments calculated for the predicted most stable tautomers of the lactam forms of the hydroxypurines (as discussed in Section VII) and which are generally the N(7)H tautomers, we come out with a rather high dipole moment ( 9 D) for 2-hydroxypurine and relatively low dipole moments for 6-hydroxypurine (2.6 D) and 8-hydroxypurine (1.4 D) (the numbers quoted come from CNDO calculations). Under these conditions the lactimization should correspond to a decrease in the dipole moment in 2-hydroxypurine (3-7 D) and to its increase in 6-hydroxypurine (3.6-5.7 D) and 8-hydroxypurine (3.2-4.6 D). Unfortunately no experimental data are available in this field. Calculations are also available for the directions of the moments (as well as for the transition moments and the HOMO s and LEMO s of all these compounds). 

Whatever be the difficulties in dealing satisfactorily with the problem of the lactam-lactim tautomerism in hydroxypurines, the predominance of the lactam tautomer granted, there remains the problem of the detailed structure of the most probable lactam form for each isomer. The problem is essentially that of the site of location of the imidazole proton. From that point of view forms 34-38 have to be considered for 2-hydroxypurine, forms 39—42 for 6-hydroxypurine (hypoxanthine), and forms 43-45 for 8-hydroxypurine. There are, in addition, some betaine tautomeric forms but these are probably of low stability and will not be considered further. Before describing the results of theoretical calculations, it may be useful to indicate that from the experimental point of view we may, in this respect, turn again for significant evidence to infrared spectroscopy... 

In complete agreement with the deductions from infrared data, the calculations estimate the tautomers 37, 40, and 43 as the most stable forms of 2-hydroxypurine, 6-hydroxypurine, and 8-hydroxypurine, respectively, followed very closely, however, by tautomers 34 and 39 for the first two isomers. Their existence as mixtures of tautomeric forms in comparable proportions seems therefore highly probable. On a relative scale the most stable of the three isomers should be the 8-hydroxy one (certainly because of the high content of its 77-electronic delocalization), which should, in fact, be appreciably more stable than the 2- or 6-isomers, which are predicted to be of comparable stability. 

In all three isomers the most stable tautomeric form involves one proton at N-7, the second one being at N-3 in 2-hydroxypurine, at N-l in 6-hydroxypurine, and at N-9 in 8-hydroxypurine. The preferential attachment of a proton at N-7 of these isomers seems thus a general feature of their structure. Although this situation agrees with the probable preeminence of the N(7)H tautomers in solution, it should not be considered as prejudging the nature of the tautomer present in the crystal of these substances, a problem which will be discussed in detail in Section XI. 

Figure 4. MECC chromatogram of the purines adenine(A), 6-methylpurine(B), 2 hydroxypurine(C), 6,6-dimethylamino-purine(D), and xanthine(E).

Methylsulfanyl)purines are good starting materials for the preparation of aminopurines. This method can be successfully employed in the synthesis of 6-substituted aminopurines, e.g. 1, and 2, from 6-(methylsulfanyl)purine and 8-(alkylamino)-2-hydroxypurines from 2-hy-droxy-8-(methylsulfanyl)purine, but presents some difficulties when the methylsulfanyl group is in the 2-position. 

Standard methods involving glycosyl halide or ester derivatives in reaction with protected heterocycles have been applied to the synthesis of various glycosyl derivatives of 5-fluoro-uracil and -cytosine, a number of nitro-imidazoles and -pyrazoles, thiadiazines and oxadiazolo-thiadiazines, and 5-methylthio derivatives of -uracil, -4-thiouracil, and -cytosine,/3-D-ribofuranosyl derivatives of 2-thio-6-azauracil, diethyl 4-hydroxypyrazole-3,5-dicarboxylate, 5-acetyl-uraeil, 2,4- and 2,5-thiazolidinediones, 4-thiomethyl-2-azapurine, 2-hydroxypurine, 3-deaza-adenine-8- C, l-deaza-8-azaguanine, imidazo-(l,2- )l,3,5-triazenes, e.g., (5), //n-benzo-guanosine, -inosine, and -xanthosine (6), and a derivative of lV-2-(i3-D-ribopyranosyl)benzotriazoie. Likewise 2-0-... 

Holy (77) described the preparation of 9-(beta-D-ribofuranosyl)-2-hydroxypurine beginning with the reaction of 5-aminocytosine with ethyl orthoformate involving several intermediates and reactants including 2-hydroxypurine and 5-nitrocytosine their TLC and on silica with chloroform and chloroform-ethanol (1 40). A (78) 9-(RS)-(2,3-dihydroxypopyl)adenine derivative has been outlined for the preparation, separation, and identification of isomeric 3-aminopropylamino and its derivatives by comparison to known substances on silica by using several solvents including 2-propanol-NH3-water, chloroform-ethanol, and chloroform-methanol. 

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