Purine 5 ,8-cyclonucleoside

The formation of purine 5, 8-cyclonucleosides and -cyclonucleotides and pyrimidine 5, 6-cyclco-nucleosides are a typical product of an oxidation at C(5 ). Because it involves an addition of an alkyl radical to the base moiety, this reaction has already been discussed in Section 5.3.1. The dAdo C(5 ) radical was generated specifically by reacting 8BrdAdo with eaq. The ensuing reactions are discussed in Section 7.2. 

Hydrogen Atom Abstraction at C5 Formation of Purine 5, 8-Cyclonucleosides... 

Evidence for the "OH induced formation of purine 5, 8-cyclonucleosides has been provided in early model studies involving nucleosides [118], nucleotides [119, 120], and isolated DNA [121]. This may be explained in terms of OH-mediated hydrogen atom abstraction from the C5 -hydroxymethyl group followed by intramolecular cyclization that occurs with a rate constant k = 1.6 x 10s s 1 in the case of... 

Belmadoui N, Boussicault F, Guerra M, Ravanat JL, Chatgilialoglu C, Cadet J. Radiation-induced formation of purine 5 ,8-cyclonucleosides in isolated and cellular DNA high stereospecificity and modulating effect of oxygen. Org Biomol Chem. 2010 8 3211-3219. 

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... 

Ikehara, M. and Maruyama, T. (1975) Studies of nucleosides and nucleotides - LXV Purine cyclonucleosides-26 a versatile method for the synthesis of purine O-cyclo-nucleosides. The... 

Ikehara, M. and Imura, J. (1981) Studies on nucleosides and nucleotides. LXXXVII. Purine cyclonucleosides. XLII. Synthesis of 2 -deoxy-2 -fluoroguanosine. Chem. Pharm. Bull., 29, 1034-1038. 

The Mitsunobu reaction has been used previously to prepare 5 -0-acylnucle-osides and nucleoside 5 -phosphates [111, 112]. With purine nucleosides, the approach failed (< 1 % yields) in the preparation of 5 -phosphates, the main product being N3,5"-cyclonucleosides resulting from an intramolecular nucleophilic attack by a purine ring nitrogen atom on the 5 -carbon atom. The predominant formation of the purine cyclonucleosides was attributed to electrostatic interactions between the phosphorus cation and the purine base which brought the reaction sites (5 and 3-N) close enough to favor cyclization [113]. 

Carbon-bridged purine cyclonucleosides have attracted attention... 

M. Ikehara, A. Hasegawa, J. Imura, Studies of nucleosides and nucleotides LXXXV. Purine cyclonucleosides 41. A new synthesis of 2 -deoxy-2-fluoro-adenosine by the use of tetrahydropyranyl protecting group. J. Carbohyd. Nucleosides Nucleotides 7 131 (1980). 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

One of the first OH-induced purine damage detected was in the 5, 8-cyclonucleotides. This lesion was later also observed in DNA (Chap. 12.5). In the following, the non-trivial case, the reactions of organic radicals with pyrimidines and purines will be discussed, and a special section will devoted to 5, 8-cyclonucleosides and nucleotides whose mechanism of formation has been found to be very complex. 

Cyclonucleosides. A typical protected cyt lopurine nucleoside (2) can be obtained by oxidation of a protected purine nucleoside (1 with LTA in refluxing benzene. 

The tandem lesion discussed above is only one example for other examples the reader is referred to the literature. For the vast literature on the formation of purine 8,5 -cyclonucleosides that also belong to that group of lesions see Ref 2. 

Many examples of compounds in which a heterocyclic ring is fused to a purine have been recorded. These include the various types of cyclonucleosides such as (210). However in this chapter a discussion of these compounds is not practical and for further details the reader should consult works devoted to nucleoside chemistry. Appropriate references are collected in Table 2. 

The fused heterocyclic rings to be discussed here have normally been produced by an intramolecular cyclization of an N(6)-, N(2)- or S-substituent onto a ring nitrogen atom in the purine nucleus and are mainly five- or six-membered systems cyclonucleosides such as (210) are of course notable exceptions and a few miscellaneous examples exist. 

The synthesis of 2 -deoxy-2 -a-fluoro purine nucleosides via cleavage of purine O-cyclo-nucleosides (see Scheme 7.2) has not been reported, presumably for the following reasons [18] (i) the synthesis of purine O-cyclonucleosides is not so easy as that of pyrimidine O-cyclonucleosides (ii) the glycosyl bond of purine nucleosides is rather unstable under severe reaction conditions such as the use of HF and (iii) it is not easy to remove the... 

A soln. of 6-amino-9-(2,3-0-isopropylidene-5-deoxy- -D-eAyr/zr<7-pent-4-enofurano-syl)purine in dry chloroform cooled, stirred, and treated dropwise at 10° with a soln. of bromine in the same solvent, and allowed to stand 12 hrs. at 0° -> 5 -bromo-5 -deoxy-2, 3 -0-isopropylidene-N3- -cycloadenosine bromide. Y 89%. -This is the first reported N3- -4 -furanose cyclonucleoside. J. R. McCarthy, Jr., R. K. and M. J. Robins, Am. Soc. 90, 4993 (1968). 

A number of purine 8,5 -imino and substituted imino cyclonucleosides have been prepared,as have a variety of 8,2 -hydrazo and oximido- bridged purines such as (23). The 2,3 -iminohexo-syluracil nucleoside (24) was produced as shown in Scheme 4 some similar cyclonucleosides were prepared and a mechanistic picture... 

Approaches to nucleoside synthesis by additions to suitably activated N-glycosides continue to receive attention. Ribofuranosyl purines have been prepared by addition of the imidazole derivative (7) to the glycosyl iminoether (8). Both a- and /3-ribosyl hypoxanthines and the corresponding 6-thio analogues were prepared in this manner. Addition of diketene to the amino-oxazoline derivative (9) gave a cyclonucleoside which was hydrolysed to the nucleoside analogue (10). Cyclization of ribopyranosyldiaminomaleonitrile... 

A paper on the hydrolysis of purine 5 -cyclonucleosides is mentioned in Section 14. 

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