Nucleosides cyclonucleosides

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). 

In a similar way, 5-O-acetylthymidine was converted into the 3-deoxy-3-iodo derivative 72 in 55% yield. In this case, the replacement of the hydroxyl group by iodine was presumed to have taken place by retention of the configuration at C-3. The first intermediate in the reaction was proposed to be the phosphonate (70) which rapidly collapses to an O-3-cyclonucleoside (71) and the latter is subsequently attacked by iodide ion to give the product 72. It was also observed (106) that treatment of nucleosides containing a cis vicinal diol grouping such as 5-0-acetyluridine with triphenylphosphite methiodide failed to provide iodinated products but gave phosphonate derivatives instead. 

Reaction of the silyl derivative of quinoline with 2-acetoxyethyl acetoxy-methyl ether in dichloroethane with stannic chloride gave a cyclonucleoside. Removal of both the acetyl and ethyl ester groups in NaOH afforded the fully deprotected nucleoside 788. Acylation of 788 could be carried out with different esters in the presence of amino Ps lipase [91SC1477 92JCR(S)216]. The 4-quinolones showed no significant antiviral activity (91SC1477). 

M. Ikebara and H. Miki, Studies of nucleosides and nucleotides. LXXXH Cyclonucleosides. (39). Synthesis and Properties of 2 -halogeno-2 -deoxyadenosines, Chem. Pharm Butt. 26 2449 (1978). 

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. 

Unequivocal chemical proof of the glycosyl configuration of nucleosides in the ribose and deoxyribose series arose from studies of the anhydronu-cleosides ( cyclonucleosides ). Levene and Tipson129 had demonstrated that 2,3-0-isopropylideneuridine may be sulfonylated to the 5-0-tosyl... 

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

A novel type of cyclonucleoside (4) is obtained from a similar oxidation of a protected pyrimidine nucleoside (3). 

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. 

Synthesis of 2 -Deoxy-2 -oc-fluoro Pyrimidine Nucleosides via Cleavage of Cyclonucleosides... 

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... 

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]. 

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... 

Analogous structures were established for the 2 -deoxynucleosides.They were not oxidized by periodate18 and could be converted into cyclonucleosides,1920 thus showing the (3 configuration. In addition the ribonucleoside uridine was converted into 2 -deoxyuridine,21 obtained by deamination of the naturally occurring 2 -deoxycytidine, via 02,2 -cyclouridine,22,23 a versatile intermediate exploited in Cambridge and elsewhere for the synthesis of 3-/I-D-arabinofuranosyl uracil (spongouridine) and other nucleosides.24 This and other cyclonucleosides are capable of a remarkable number of useful transformations. 

A new class of 2,4 -0-cyclonucleoside (29) has been obtained as outlined in Scheme 7 4 -substituted nucleosides prepared from this compound included the methoxy derivative (30), obtained using methanolic silver nitrate, and hence the uridine analogues (31) by reduction. ... 

High-yielding stereoselective syntheses have been reported for psicofuranine and 9-oi-D-fructofuranosyladenine 1-6-D-psico-furanosyluracil (16) was also prepared in an improved procedure, and converted, via a cyclonucleoside, to the fructofuranosyl nucleoside (17) as in Scheme 5. ... 

In a series of pyrimidine cyclonucleosides, the magnitude of J(C1, H1 ) varies quantitatively with glycosidic bond conformation. Measurement of this coupling consteuit in pyrimidine nucleosides can be used to determine the range of allowed syn and anti conformations.In riqld cvclonucleosldes of adenosine,... 

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... 

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