Cyclonucleosides formation

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. 

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. 

The formation of the cyclonucleosides shown below (for their synthesis see Ro-mieu et al. 1999b) shows that the addition of the C(5 ) radical can also add to the C(5)-C(6) Thy double bond [the corresponding Cyd case has been discussed... 

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. 

Protected /3-D-ribofuranose and 3(2//)-pyridazinones gave the N-glucosides, whereas 4-amino-3-chloro-6(l//)-pyridazinone afforded the O-glycoside (87MI27). In the formation of pyridazine cyclonucleosides, either the 2 - (75) or 5 -hydroxy group (76) was involved in ring formation (83JOC3765). 

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]. 

Goodman has reviewed neighboring-group participation in Volume 22 of this Series,366 and this subject will therefore not be discussed comprehensively in the present article. However, Goodman specifically excluded from his review the formation of anhydro sugars by oxide ion displacements, and also the formation of anhydronucleosides ( cyclonucleosides ). These topics will therefore be discussed, together with ring contractions and alkoxyl participations, because most of the literature on these subjects has not been reviewed previously. 

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. 

The oxazolinone 107, a new recoverable chiral auxiliary that gives a high level of asymmetric induction in model aldol reactions and Diels-Alder cycloadditions (in which the reactant is connected to the auxiliary by -acylation), has been synthesized from L-gulonic acid. The key step in its synthesis was the thermal intramolecular nitiene insertion shown in Scheme 21. The formation of oxazolinethiones on hydrolysis of isothiocyanato-sugar derivatives is covered in detail in Chapter 9, section 3.3. Base-catalysed reaction of StS-O-isopropylidene-D-xylofuranosylamine with P-isothiocyanato-alkanals led to tricyclic derivatives such as 108, considered as cyclonucleoside analogues. ... 

The 3,3 -cycloadenosine derivative (605) and 5 -chloro-5 -deoxyadenosine 2, 3 -sulphate (606) were formed when adenosine reacted with sulphuryl chloride in acetonitrile. Solvolysis of (606) in aqueous ethanol resulted in opening of the pyrimidine ring and formation of the cyclonucleoside (607). 3,5 -Cycloadenosine was synthesized from 5 -chloro-5 -deoxyadenosine, which was prepared by treating adenosine with thionyl chloride in HMPT. 

A full account has been given of the formation of 5 -0,8-cycloadenosine derivatives by oxidation of the parent compounds with lead tetraacetate (see Vol. 18 p. 195),38 and 5 -0,6-methanouridine (20), a new type of pyrimidine cyclonucleoside, has been prepared as outlined in Scheme 4 conformational studies were also carried out on this system.39 The previously-reported instability of uridine 6-carboxaldehyde has been reinvestigated, and it has been found that the compound and its derivatives have a propensity to hydrate to gem-diols, and, in the case of the parent compound, form the cyclic hemiacetal 21. 0... 

When 2 -deojreact with acetyl hypofluorite. adduct (10) was formed together with the alternative cis-diastereomer. Treatment of (10) with ferric chloride in dry acetonitrile gave the Q, 5 -cyclonucleoside (11), and the other diastereomer behaved similarly. Similar reactions occur with uridine and ara-U. but in the latter case some 0 , 2 -cyclonudeoside formation is also found.37... 

Chemical proof for the cis relationship of the base and S -CHjOH (normal nucleoside numbering) in these compounds came from the formation of cyclonucleosides through the treatment of isoddN 5 -tosylates with DBU (Scheme 11). 

There are several reports that describe attempts to favor the formation of P- over a-D-2 -deoxynucleosides.36-39 The availability of 33a prompted us to use the chirality at C-4 to deliver the base in a stereospeciflc manner from the P side. Compound 33a was converted via the tosylate to the iododerivative 33b, which was S-alkylated with 2-thiouracil to give 34. TMS triflate-catalyzed cyclization in acetonitrile furnished the 2S,S -cyclonucleoside 35 in 65% yield. While Raney nickel desulfurization of 35 furnished 36, an unprecedented reaction took place where palladium hydroxide catalyzed a stereospecific... 

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