Halogenated purines

Halogenated purines. 8BrdAdo has been used to study some of the steps in the cyclization reaction that yields the purine cyclonucleosides/tides (Flyunt et al. 2000 Chatgilialoglu et al. 2003). Upon the reaction of eaq, the very reactive vinylic radical at C(8) is formed [reaction (238) k= 1.6 x 10 dm3 mol-1 s 1] which undergoes rapid H-abstraction from the hydroxymethyl group at C(5 ) [reaction (239)]. In neither of these reactions are radicals formed which strongly absorb in the accessible UV/Vis range. Upon addition of the C(5 ) radical to C(8) [reaction (239) k = 1.6 x 105 s-1], an aminyl radical is formed whose UV/Vis spectrum is... 

Halogen atoms in nucleosides can be replaced photochemically by sulphur as has been demonstrated in the photoinduced alkylthiolation of halogenated purine nucleosides433,749, in the synthesis of 2-(methylthio)adenosine from 2-iodoadenosine750 and in the photochemical formation of a cysteine-uracil adduct from 5-bromouracil and A-acetylcysteine methyl ester435. Photochemical synthesis of phosphonopyrimidine and phosphonopurine nucleosides by reaction of bromonucleosides with triethyl phosphite has also been reported751. 

An unusual nucleoside, kumusine (85), has been reported from the Indonesian marine sponge Theonella sp. [92]. Kumusine (85) represents the first natural occurring halogenated purine nucleoside containing an alkylated sugar, 2-methyl-5-deoxy ribose, that also represents a new... 

It has been stated that many halogen-free compounds, e.g., certain derivatives of pyridine and quinoline, purines, acid amides and cyano compounds, when ignited on copper oxide impart a green colour to the dame, presumably owing to the formation of volatile cuprous cyanide. The test is therefore not always trustworthy. The test is not given by duorides. 

Purine, 1,6-dihydro-8,9-dimethyl-6-thioxo-synthesis, 5, 583 Purine, 2,6-dimethoxy-synthesis, 5, 596 Purine, 2,6-dimethoxy-7-methyl-rearrangement, 5, 558 Purine, 2,7-dimethyl-halogenation, 5, 547 Purine, 7,9-dimethyl-UV spectra, 5, 517 Purine, 8,8-dimethyl-synthesis, 5, 580 Purine, 6-dimethylamino-mass spectra, 5, 519 occurrence, 5, 600 Purine, 6-dimethylamino-9-benzyl-alkylation, 5, 531 Purine, 3,7-dimethyl-6,8-dioxo-methylation, 5, 534 Purine, 6,8-dioxo-alkylation, 5, 534... 

Purine, 9- -D-ribofuranosyl-6-selenoxo- 1,6-dihydro-synthesis, 5, 597 Purine, 6-thiocyanato-acylation, 5, 559 Purine, 2-thioxo-synthesis, 5, 589 Purine, 8-thioxo-iodination, 5, 559 synthesis, 5, 577, 597 Purine, 2-thioxo-2,3-dihydro-synthesis, 5, 572 Purine, 6-thioxo-1,6-dihydro-acylation, 5, 559 dethiation, 5, 558 halogenation, 5, 559 hydrolysis, 5, 560 methylation, 5, 535 oxidation, 5, 560 synthesis, 5, 572, 596 Purine, 8-thioxo-7,8-dihydro-acylation, 5, 559 Purine, 2,6,8-trichloro-alkylation, 5, 530 amination, 5, 562 reactions, 5, 561, 562 with hydriodic acid, 5, 563 with pyridine, 5, 562 synthesis, 5, 598 Purine, 2,6,8-trichloro-7-methyl-synthesis, 5, 557 Purine, 8-trifluoromethyl-synthesis, 5, 574... 

Although purine nucleosides can frequently be halogenated at the vacant imidazole carbon (see above), AMialogenosuccinimides in acetic acid tend to promote intramolecular cyclizations instead. It has been demonstrated that 2-bromoadenosine is not an intermediate in this process (Scheme 55), which is believed to involve initial attack by positive halogen at N-3. 

The preparation of purine derivatives substituted at the C-2 position via amine displacement of a halogen is known as a difficult reaction step requiring several days of reaction time. However, Al-Obeidi and coworkers have recently prepared 2,6,9-trisubstituted purines on soUd-phase by employing a synthetic route in which the critical step was performed with microwave irradiation (Fig. 37) [62]. PS resin-bound 2-iodosubstituted purine was treated with diethanolamine or propanolamine in NMP with microwave irradiation at 200 °C for 30 min. Trifluoroacetic acid-mediated cleavage resulted in the 2-amino substituted purines in 45-59% yields and 77-89% purities. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

Reductive removal of halogen substituents has been of value in the synthesis of pyrimidines and purines since the time of Fisher (1899). Natural purines were de-oxygenated in a sequence of reactions involving the replacement of hydroxyl by chlorine through the reaction with phosphorus pentachloride and the reduction using zinc dust and water [152], 2-Chloropurines 45 are not reduced under these conditions. The 2-iodopurines are however reduced by zinc and water [152]. The elec-... 

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. 

This chapter discusses the transition metal catalyzed functionalization of such systems that fall outside the topic of Chapters 6 and 7, as well as certain other compound classes (e.g. purines, pyrones). In contrast to the abundant literature of the chemistry of five and six membered systems, the transition metal catalyzed transformations of other heterocycles have not been studied so far in the same depth, probably due to the limited availability of their halogen derivatives compared to haloazines and haloazoles. Purine compounds and their structural analogues constitute an exception, since their biological importance proved to be a strong drive for synthetic chemist worldwide.1... 

The exchange of a halogen to a classical nitrogen or oxygen nucleophile usually proceeds readily on the purine skeleton, without the necessity of using a transition metal catalyst. There are certain cases, however, where the palladium catalyzed carbon-heteroatom bond formation might take preference over noncatalysed methods. Inosine derivatives, for example,... 

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