2- Azapurine nucleosides

Ab initio molecular orbital calculations on these systems have been confined to the 1,2,3-triazolo[4,5-d]pyrimidines (7), the so-called 8-azapurines , and references to this subject may be found in the previously mentioned review <86AHC(39)ii7>. In 1989, quantum mechanical perturbation methods have been used to study the activity of 8-azapurine nucleoside antibiotics in transcription processes <89Mi 7i3-oi>. The l,2,3-thiadiazolo[5,4-d]pyrimidine derivative (51), a rearrangement product of 8-aza-6-thioinosine, has been used in a molecular modeling study of the antitumor activity of sugar derivatives of pyrimidopyrimidines <89PNA(86)8242>. 

Treatment of the silver salt of methyl imidazole-4,5-dicarboxylate (138) with acylglycopyranosyl halides gave the imidazole nucleosides (139) which, on reaction with ammonia, were deblocked and converted to the diamides (140). Reaction of the diamides (140) with alkaline hypobromite (the Hofmann reaction) gave mixtures of the 7- and 9-nucleosides (141 and 142), with the 9-isomer predominating. In fact, in the early investiga-tions- of this reaction, only the 9-isomer w as isolated but, in the preparation of 8-azapurine nucleosides by the same method,both... 

C. W. Smith, R. W. Sidwell, R. K. Robins, and R. L. Tolman, Azapurine nucleosides. 2. Synthesis and antiviral activity of 7-amino-3-a-D-arabinofuranosyl-v-triazolo[4,5-J pyrimidine and related nucleosides, J. Med. Chem., 15 (1972) 883-887. 

The structures of the or// o-azapurine nucleosides would be expected to be essentially similar to those of the azapyrimidine nucleosides discussed above. The only true 8-azapurine nucleoside whose structure has been determined to our knowledge is 8-azaadenosine (8-AAD) [18], a sample of which was kindly donated by Dr John Montgomery and whose structure is depicted in Figure 8. The absence of the proton... 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

The carboacyclic nucleoside analogs considered under this section could be also considered in Section III,G as a component resulting from two bond disconnections. However, it is preferable to consider them as acyclovir analogs. The carboacyclonucleosides having purine 934 and 8-azapurine rings 935 have been prepared starting by reaction of 2-amino-... 

Purines show typical absorption spectra which are useful for the identification and the determination of their structure tautomeric equilibria can also be studied. By comparison of the spectra of natural and synthetic derivatives of purines, the N9 glycosylic linkage was established for nucleosides. The relatively simple spectra of purines show two main bands. Purine shows maxima around 220 nm and at 263 nm in neutral solution. Since the imidazole ring has no characteristic UV absorption, the spectra of purines and pyrimidines show similarities. Similar observations have been made for 7-deazapurines, 8-azapurines etc. In the series of adenine hypoxanthine, and xanthine (at pH 6) only one maximum is observed guanine, isoguanine, and purinc-2,6-diamine show two maxima. 

Moreover, it has recently been recognized, that 8-azapurines and their nucleosides 11 and 12 show intense fluorescence. ... 

Glycosides. Because of their possible therapeutic value in acting as antagonists of the natural purine riboades (nucleosides), interest remains high in attempts to improve yields of the 8-azapurin-9-/ -D-ribosides, as weU as analogs with other sugar residues. 

The ribofuranosyl-oxazolidine thione(6) has been used as a source of a-ribofuranosyl imidazole derivatives leading to purine and 2-azapurine a-nucleosides. D-Arabinose or D-ribose reacts with cyanamide to yield isomeric 2-amino-l,2-oxazolines (7), which are useful intermediates for nucleoside synthesis.The P-N ylide (8) has been used to prepare tetrazole nucleosides by conversion to the diimide (9) with isocyanate and subsequent azide cyclo addition.Conversely, glycosyl azides undergo cyclo-... 

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