Purine nucleoside, alkylation

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

Ultraviolet (UV) spectroscopy does not tend to be the method of choice for structure determination, but a list of UV absorptions was given in the review by Knowles <1996CHEC-II(7)489>. Fluorescence properties and triplet yields of [l,2,3]triazolo[4,5-r/ pyridazines in various solvents have been reported <2002JPH83>. These heterocyclic systems were found to be photochemically very stable. In a recent paper, Wierzchowski et al. studied the fluorescence emission properties of 8-azaxanthine ([l,2,3]triazolo[4,5-r/ pyrimidine-5,7-dione) and its A -alkyl derivatives at various pH s <2006JPH276>. For the 8-azaxanthines, an important characteristic of emission spectra in aqueous solutions was the unusually large Stokes shift. Since 8-azaxanthine is a substrate for purine nucleoside phosphorylase II from Escherichia coli, the reaction is now monitored fluorimetrically. The fluorescence properties of [l,2,3]triazolo[4,5-r/ -pyrimidine ribonucleosides were earlier described by Seela et al. <2005HCA751>. 

Trifluoromethylation is the most important perfluoroalkylation reaction. Kobayashi and co-workers reported the trifluoromethylation of aryl, vinyl, alkyl halides with trifluoromethyl iodide in the presence of copper powder in aprotic solvents such as HMPA at 120-150 °C [83,84], and this methodology has been applied to the preparation of fluorinated pyrimidine and purine nucleosides [85,86] (Scheme 27). 

Such a catabolic reaction is indeed excluded in 6 alkyl purine derivatives. The parent compound of this group, 6-methylpurine, is known for its cytotoxicity its libera tion from the 2 -deoxyribonucleoside by purine nucleo side phosphorylases is used for detection of mycoplasma in cell cultures.19 It is highly potent and toxic to nonproliferating and proliferating tumor cells. Recently, the use of cytotoxic bases liberated by purine nucleoside phosphorylases such as 6-methylpurine was proposed as a novel principle in the gene therapy of cancer.20... 

Hirota, K. Kitade, Y. Kanbe, Y. Maki, Y. Convenient Method for the Synthesis of C-Alkylated Purine Nucleosides Palladium-Catalyzed Cross-Coupling Reaction of Halopurine Nucleosides with Trialkylaluminums. J. Org. Chem. 1992, 57, 5268-5270. 

The (ft)-4-phenyl-2-oxazolidinonc auxiliary was used in the process development and scale up of Novartis purine nucleoside phosphorylase inhibitor PNP405 (16) (Scheme 23.2).43 Asymmetric alkylation of 17 with bromoacetonitrile provided a 7 1 diastereoisomeric ratio of crude 18. Recrystallization afforded 18 in 80% yield and >99% de. Simple addition of sodium borohydride in tetrahydrofuran (THF)-water at room temperature44 resulted in the desired y-cyano alcohol 19 and recovery of the auxiliary. 

Clearly, the most widespread nucleophilic reaction by heteroatoms is alkylation at ring nitrogen atoms. It is unsurprising that the very great interest in nucleosides of pyrrolo[2,3-d]pyrimidines, as deaza analogues of purine nucleosides, dominates this field. Selected examples of this chemistry... 

Recently a valuable route to 8-alkyl- or acyl-purine nucleosides has involved the reaction of an unsubstituted or 8-halogenopurine with butyllithium and an appropriate alkyl or acyl halide, including ethyl chloroformate, when excellent yields of the 8-substituted purine nucleosides are produced <79TL2385). 

The results of various alkylations of purines and purine nucleosides are collated in Table 44. Table 44. Alkylation of Purines and Purine Nucleosides by Various Methods... 

By Alkylation of the Ring Nitrogen Atoms of Purine Nucleosides... 

Several early studies of the methylation of purine nucleosides that reported a variety of results have been reviewed. Bredereck and coworkers have stated that the products obtained from adenosine and guanosine vary with the pH of the reaction solution. More recently, an interest in the mechanism of anticancer action of the so-called alkylating agents, such as nitrogen mustard ( HN2 )j led to an investigation of the action of dimethyl sulfate on guanosine 5-phosphate, 2-deoxyguanosine 5-phos-... 

The reaction of other alkylating agents with purine nucleosides, nucleotides, or nucleic acids gives results similar to those described above. ... 

Purine nucleosides have also been alkylated in the 2-position using tetraalkylstannane reagents (Scheme 37). Methyl- and ethyl-substituted... 

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