Nucleoside analogs, synthesis

Poonian, M S, Nowoswiat, E F, A novel precursor for the synthesis of C-nucleoside analogs. Synthesis of the C-nucleoside analogs of ribavirin, bredinin, and related compounds, J. Org. Chem., 45, 203-208, 1980. 

New nucleoside analogs, synthesis, and biological properties 00PAC1705. 

Cui L, Locatelli L et al (1997) Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells. J Pharmacol Exp Ther 280(3) 1228-1234 Dal Pan GJ, Glass JD et al (1994) Clinicopathologic correlations of HIV-l-associated vacuolar myelopathy an autopsy-based case-control study. Neurology 44(11) 2159-2164 Dalakas MC (2001) Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst 6(l) 14-20 Dalakas MC, Semino-Mora C et al (2001) Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2 3 -dideoxycytidine (ddC). Lab Invest 81(11) 1537-1544... 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

Anhydrohexonic acids of this type have the desired cis-orienta-tion of the side-chains at C-2 and C-5, and they may be regarded as versatile intermediates in the synthesis of C-/3-i>pentofuranosyl heterocycles. Indeed, the synthesis of a C-nucleoside analog based on this approach has been reported31 (see Section IV,4,d). The inversion of configuration of C-3 in 15 would, on the other hand, lead to the D-ribo configuration, found in the natural C-nucleosides. 

The reaction of silyl ketene acetal addition to nitrones has been used for the synthesis of optically active (2S,3S)-benzoyl- and /V- oc-phenyl isoserine (636a) of isoxazolidine nucleoside-analog of thymine polyoxine C(636b) and of... 

Sulfoxides have also been used in the synthesis of nucleoside analogs (Scheme 3.2). Chanteloup and Beau reported the synthesis of ribofuranosyl sulfoxide 13 and its use in the glycosylation of a series of silylated pyrimidine and purine bases.7 Although 16 is not an anomeric sulfoxide, its reaction with cytosine derivative 17 is conceptually related.8... 

Casu, F., Chiacchio, M.A., Romeo, R. and Gumina, G., Chiral synthesis of heterosubstituted nucleoside analogs from non-carbohydrate precursors. Curr. Org. Chem., 2007, 11, 1017-1032. 

Sulfur compounds with divalent sulfur functionalities are much more prone to dioxirane oxidation on account of their higher nucleophilicity compared to the above-presented oxygen-type nucleophiles. Examples of this type of dioxirane oxidation abound in the literature. Such a case is the oxidation of thiols, which may be quite complex and afford a complex mixture of oxidation products, e.g. sulfinic acids, sulfonic acids, disulfides, thiosulfonates and aldehydes , and is, therefore, hardly useful in synthesis. Nevertheless, the oxidation of some 9i/-purine-6-thiols in the presence of an amine nucleophile produces n >( -nucleoside analogs in useful yields (equation 19). This reaction also displays the general chemoselectivity trend that divalent sulfur functionalities are more reactive than trivalent sp -hybridized nitrogen compounds P. 

In a synthesis of nucleoside analogs, the sodium salts of phthalazine-l,4-dione, phthalazin-l(2//)-one, and two pyridazin-3(2//)-ones, prepared with sodium hydride in DMF, were alkylated with ( )-2,3-0-isopropylidene-l-0-(4-toluenesulfonyl)glycerol by a nucleophilic substitution of the tosyloxy group <1999AP327>. 

Mechanism of Action A guanosine nucleoside analog that inhibits hepatitis B viral polymerase, which blocks reverse transcriptase activity. Therapeutic Effect Interferes with viral DNA synthesis. 

Tenofovir is an acyclic nucleoside phosphonate (ie, nucleotide) analog of adenosine (Figure 49-2). Like the nucleoside analogs, tenofovir competitively inhibits HIV reverse transcriptase and causes chain termination after incorporation into DNA. However, only two rather than three intracellular phosphorylations are required for active inhibition of DNA synthesis. 

Purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1) catalyzes the reversible phosphorylysis of ribonucleosides and 2 -deoxyribonucleosides of guanine, hypoxanthine, and related nucleoside analogs [1]. It normally acts in the phosphorolytic direction in intact cells, although the isolated enzyme catalyzes the nucleoside synthesis under equilibrium conditions. Figure 1 shows the chemical reaction. 

S ATP -I- dCMP <4> (<4> the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis [25] <4> the enzyme catalyses an important step in the phosphorylation of UTP, CTP and cCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies [26]) (Reversibility <4> [25, 26]) [25, 26]... 

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