6-Methoxy-9- purine

A -Methyladenosine (XXV) (227, 239, 250], fV-methy 1-2 -deoxyadenosine (XXVI) [57], 3 -amino-V-methyl-3-deoxyadenosine [254], and 6-methoxy-purine ribonucleoside (LII) [63, 234, 241] are all good inhibitors of adenosine deaminase and fV-methyladenosine (XXV) has been used in combination with 9-/3-D-arabinofuranosyladenine (XIX) to increase its activity [255]. A number of 2-substituted A -methyladenosines [61] and 9-substituted adenines (see reference 256 and earlier papers by Schaeffer) are also inhibitors of the enzyme. 

Calf duodenal adenosine aminohydrolase affects enzymic hydrolysis of a wide variety of 6-substituted purine derivatives as well as analogs of adenosine with alteration in the purine ring and sugar moiety (Table IV) (65, 65a, 67, 70, 71, 112). Although not noted in Table IV, AMP, ADP, and ATP are not substrates. The hydrolysis of the 6-methoxy-purine derivative in H2180 occurs between C-6 and oxygen (113) consistent with the observed back incorporation of 180 from H2180 into inosine as catalyzed by both calf duodenal and Takadiastase non-... 

The insufficient stability of RNA, mentioned above, limits the use of RNA aptamers. However, some established techniques yield nuclease-resistant aptamers. One alternative is called the Spiegelmer approach [29], another method involves incorporation of 2 -methoxy purine nucleotides [30]. 

Thus using a t-butyl peracetate and a 450 W mercury lamp as a source of methyl radicals it was shown that in acid solution hypoxanthine, 6-methoxy- and 6-methylthio-purines gave mainly the C-8 methyl derivative whereas 3-methylhypoxanthine, 3-methyl-6-methoxy-purine and 3-methyl-6-methylthiopurine gave mainly the C-2 methyl derivatives. The results tend to be reversed at higher pH (79JOC1450). 

Very recently, a low-temperature NMR study of tautomerism in purine derivatives has been conducted. The temperature dependences of the H NMR spectra were studied in DMF- /j solution. Two sets of signals were observed in the NMR spectra of the two purine derivatives at 213 K, whereas at laboratory temperature, there was only a single set of signals, reflecting the time-averaged contribution of the two components. Based on the characteristic values of the and N chemical shifts and the three-bond scalar coupling constants, the two components were determined to be the N -H and N -H tautomers. The NMR parameters obtained for the two tautomers of 6-methoxy purine are shown in Fig. 12. 

Jones, L.A., Moorman, A.R., Chamberlain, S.D., et al (1992) Di- and triester prodrags of the Varicella-Zoster antiviral agent 6-methoxy-purine arabinoside. J. Med. Chem. 35 56-63. 

Purine, 6-iodo-alkylation, 5, 530 synthesis, 5, 563, 597 Purine, 6-iodo-9- -D-(2,3,5-tri-0-acetyl)ribofuranosyl-synthesis, 5, 598 Purine, 9-isopropyl-deuterium-hydrogen exchange, 5, 527 Purine, 9-(2,3-0-isopropylidene-/3-D-ribofuranosyl)-6-methoxy-synthesis, 5, 584 Purine, 6-mercapto-biological activity, 5, 604 metabolism, 1, 237 as pharmaceutical, 1, 159 tautomerism, 5, 509 Purine, 2-methoxy-synthesis, 5, 596 Purine, 6-methoxy-irradiation, 5, 543 riboside... 

NMR, 5, 513 UV spectra, 5, 517 Purine, 8-methoxy-UV spectra, 5, 517 Purine, 6-methoxy-3-methyl-hydrolysis, 5, 558 irradiation, 5, 543... 

Purine, 6-methoxy-9-methyl-hydrolysis, 5, 558 Purine, 1-methyl- H NMR, 5, 511 synthesis, 5, 594 Purine, 2-methyl-amination, 5, 542 mass spectra, 5, 519 synthesis, 5, 593 Purine, 3-methyl- H NMR, 5, 511 occurrence, 5, 598 synthesis, 5, 586, 595 Purine, 6-methyl-amination, 5, 542 mass spectra, 5, 519 methylation, 5, 529 oxidation, 5, 539 1-oxide... 

CN L-valine 2-[(2-amino-l,6-dihydro-6-oxo-9//-purin-9-yl)methoxy]ethyl ester monohydrochloride... 

Qmino-l,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl N-[(benzyloxy)corbonyl]-L valinate (I)... 

Nucleobases, including 9-methyl-, 9-ethyl-, 1,9-dimethyl-guanine and 2-amino-6-methoxy-9-methylpurine, form complexes of the type Au(N)Cl3 when reacted with [AuCU] in water at pH 3—4. Binding of a AuCh unit to the N (7) position of the purine ring was confirmed by X-ray crystallography [26]. 

Mahmoudian, M., Eaddy, J. and Dawson, M., Enzymic acylation of 506U78 (2-amino-9-/ -D-arabinofuranosyl-6-methoxy-9JS-purine), a powerful new anti-leukaemic agent. Biotechnol. Appl. Biochem., 1999, 29, 229-233. 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

Scheme 7.17 Enzymatic acylation of 2-amino-9- 3-D-arabinofuranosyl-6-methoxy-9H-purine (Glaxo Wellcome).

Evidence for the formation of Meisenheimer-type adducts from a purine system has been obtained by Liotta in two cases.43 The addition of t-BuO to 6-(2-hydroxyethoxy)-9-methoxymethyIpurine in t-BuOH, as monitored by H-NMR spectroscopy, causes an upfield shift of both pyrimidine and imidazole ring protons and the conversion of two absorptions of the methylene protons of the CH2CH2OH group to a broad absorption of the dioxolane ring, in agreement with the formation of the spiro adduct 19. Similarly, adduct 20 was formed from 6-methoxy-9-methoxymethylpurine by slow reaction with MeCT in 7-BuOH. 

One obvious problem with our choice of model sugar is that Cl is connected to a methoxy group in place of the nitrogenous base that would be found in nucleic acids. This clearly introduces a bias at the HI position that needs to be corrected for. Based on results discussed below, we have added 0.32 ppm from the reference shift for HI in Table 1 for pyrimidines, and have subtracted 0.20 ppm for purines. This difference of 0.52 ppm in HI shift between purines and pyrimidines is close to the value of 0.44 ppm extracted from an empirical DNA database (7). 

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