Nucleosides derivatives

Purine Nucleoside Derivatives. A number of purine nucleoside analogues are also found to be active against several DNA vimses (Fig. 3). The clinically active antiviral drug ara-A (9-P-D-arabinofuranosyladenine [5536-17-4] vidarabine, 23) is active against a number of DNA vimses in vivo and also inhibits certain RNA tumor vimses which repHcate through a DNA intermediate (43). Ara-A, was first synthesized in 1960 (44) and later... 

NH3/MeOH or NH3/H2O, 78% yield. In nucleoside derivatives the meth-oxyacetate is cleaved 20 times faster than an acetate. It can be cleaved in the presence of a )enzoate. 

Eunctionalized supramolecular systems based on monolayers of bioactive compounds (macrocyclic ionophoric peptides, crown ethers, nucleoside derivatives) 98MI12. 

C-Nucleosides derived from simple aromatic hydrocarbons 97SL341. 

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). 

Adenosine Receptors. Figure 1 Structures of widely used AR agonists, both nonselective and selective. Affinities/potencies at the ARs are found in Table 2. (a) Nucleoside derivatives that are either nonselective or selective for A receptors (1-12). (b) Nucleoside derivatives that are selective for A2a. A2a/A2b (mixed), or A3 receptors (13-19). 

WO 8 911 277 (Georgia State Univ. Found. appl. 30.11.1989 USA-prior. 23.5.1988). nucleoside derivatives ... 

This methodology has also been applied to the synthesis of nucleoside derivatives, which are used in the preparation of drugs against AIDS (Eq. 7.85).130... 

A light-induced ring expansion of the tetrazolo-uracil 147 afforded ready access to the ring expanded 57f-l,3,5-triazepine-2,4-dione nucleoside derivative 148 in 80% yield <06JOC1742>. 

Esterification of 5 -nucleoside derivatives with N-(aminoacyl)-imidazoles yields 2 - and 3 -(aminoacyl) derivatives and proceeds with apparently little selectivity169,170 this is not surprising in view of the facile, base-catalyzed, ester migration that may occur in 2 (3 )-esters of the D-ribofuranose system (see Section VII,1). 

The same synthetic scheme was applied to synthesize nucleoside analogues with natural or modified base, starting from a- and p-D-xylo-17 and p-D-ura/uHO-derivatives.105 Grouiller also used the procedure with p-D-fructose to prepare nucleoside derivatives.18 However, the fragility of the oxazoline intermediate and low yields obtained limited the methodology. 

Other sulfide photoreactions result when appropriate nucleoside derivatives are photolyzed. Upon irradiation in acetonitrile, 9-[5-deoxy-2,3-0-isopropylidene-5-(phenylthio)-/3-D-ribofuranosyl]-adenine (53) is converted into the anhydronucleoside 8,5 -anhydro-(5 -deoxy-2, 3 -0-isopropylidene-adenosine) (55) in 66% yield.111 Similar reactions were observed when other sulfur-containing nucleosides were irradiated (see Table XIII). The reaction of the sulfide 53... 

Photochemical Reactions of Sulfur-Containing, Nucleoside Derivatives... 

Lolk L, Pohlsgaard J, Jepsen AS, Hansen LH, Nielsen H, Steffansen SI, Sparving L, Nielsen AB, Vester B, Nielsen P. (2008) A click chemistry approach to pleuromutilin conjugates with nucleosides or acyclic nucleoside derivatives and their binding to the bacterial ribosome. J Med Chem 51 4957-4967. 

Bi analogues. Also omitted are the phosphorothioic acid derivatives, such as the insecticide diazinon, and related compounds. Unnatural nucleoside derivatives have been given only brief mention, since the base, rather than the sugar, is our target in this review. 

In biological methylation, the 5-methyl group of the amino acid L-methionine is used to methylate suitable O, N, S, and C nucleophiles. First, methionine is converted into the methylating agent S-adenosylmethionine (SAM). SAM is nucleoside derivative (see Section 14.3). Both the formation of SAM and the subsequent methylation reactions are nice examples of biological Sn2 reactions. 

Aciclovir is a member of a group of nucleoside derivatives termed acyclonucleosides, in that there is an incomplete sugar ring. The structural relationship to 2 -deoxyguanosine should be very clear. Aciclovir is converted into its monophosphate by the viral enzyme thymidine kinase - some viruses also possess enzymes that facilitate their replication in the host cell. The viral enzyme turns out to be much more effective than that of the host cell, and conversion is, therefore, mainly in infected cells. The monophosphate is subsequently converted into the triphosphate hy the host cell enzymes. Aciclovir triphosphate inhibits viral DNA polymerase, much more so than it does the host enzyme, and so terminates DNA replication. 

SAM, S-adenosylmethionine, has been encountered as a biological methylating agent, carrying out its function via a simple Sn2 reaction (see Box 6.5). This material is a nucleoside derivative formed by nucleophilic attack of the thiol group of methionine on to ATP (see Box 6.5). It provides in its structure an excellent leaving group, the neutral S-adenosylhomocysteine. 

Cyclopropane ring formation has been achieved by electrochemical reduction of the nucleoside derivative 17 [95]. Very highly strained cyclopropanes 18 [90] and... 

An extension of this methodology was used In another approach (16) to the octosyl acids and ezomyclns (Figure 10). In this sequence, D-galactose was transformed Into the 2-0-acetyl derivative 57. Transformation to the acyclic nucleoside derivative and selective oxidation then gave sulfoxide 58. Elimination afforded the trans olefin 59 whereupon solvolysis followed by epoxldatlon and acid-catalyzed cycllzatlon produced and In a 1 2 ratio respectively. The H-NMR spectra showed each to contain a l, 2 -trans configuration, and that the minor Isomer was the required 6-D-nucleoslde, while the major product was the a-D-nucleoslde. 

The 5-fluorocytosine (flucytosine) is an inhibitor of sterol C-14 demethylase, an enzyme involved in the biosynthesis of ergosterol, an element of fungal wall. It is marketed as an anti-fungal agent, whereas nucleoside derivatives of the... 

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