122621-07-2Relevant articles and documents
Radical mediated synthesis of 3'-α-C-allenyl-2',3'-dideoxythymidine as a non-polar analogue of AZT
Becouarn,Czernecki,Valery
, p. 307 - 309 (1995)
The synthesis of the novel modified nucleoside (1) exhibiting the 1,2- propadienyl [allenyl] group at the 3'-α-position is described. The 3'-C-C bond was formed by radical reaction between triphenylprop 2-ynylstannane (2) and the 3'-bromo(iodo)-2',3'-dide
Stereocontrolled Syntheses of Deoxyribonucleosides via Photoinduced Electron-Transfer Deoxygenation of Benzoyl-Protected Ribo- and Arabinonucleosides
Wang, Zhiwei,Prudhomme, Daniel R.,Buck, Jason R.,Park, Minnie,Rizzo, Carmelo J.
, p. 5969 - 5985 (2007/10/03)
The stereocontrolled, de novo syntheses of β-2′-deoxy-, α-2′-deoxy-, β-3′-deoxy-, and β-2′,3′-dideoxyribonucleosides are described. Strategically protected ribose, arabinose, and xylose glycosylation precursors were synthesized bearing C2-esters capable of directing Vorbrueggen glycosylation. The key step is the regioselective deoxygenation of the desired hydroxyl group as either the benzoyl- or 3-(trifluoromethyl)benzoyl derivative. This deoxygenation is accomplished via a photoinduced electron-transfer (PET) mechanism using carbazole derivatives as the photosensitizer. The syntheses of the desired deoxynucleoside generally proceed in three steps from a common, readily available precursor.
Radical Mediated Synthesis of 3'-α-C-allenyl-2',3'-dideoxythymidine as a non-polar analogue of AZT
Becouarn, Stephan,Czernecki, Stanislas,Valery, Jean-Marc
, p. 873 - 876 (2007/10/02)
The 1,2-propadienyl (allenyl) group was selectively introduced at the 3'-α-C position by free radical C-C bond formation reaction involving triphenylprop-2-ynylstannane and protected 2',3'-dideoxy-3'-halogenothymidine.
Synthesis and in vitro evaluation of some modified 4-thiopyrimidine nucleosides for prevention or reversal of AIDS-associated neurological disorders
Palomino,Meltsner,Kessel,Horwitz
, p. 258 - 263 (2007/10/02)
Oxygen-sulfur exchange at the C-4 carbonyl of several modified pyrimidine, including 3'-azido-3'-deoxythymidine (AZT), is described in an effort to enhance the lipophilicity and, thereby, the delivery to the central nervous system of the sulfur analogues without compromising the anti-HIV activities of the parental structures. Preparation of 3'-azido-3'-deoxy-4-thiothymidine (3) proceeded from 4-thiothymidine (1) and utilized the same methodology developed for the initial synthesis of AZT. Thiation of 2',3'-didehydro-3'-deoxythymidine (4a) and 2',3'-didehydro-2',3'-dideoxyuridine (4c) was carried out with Lawesson's reagent on the corresponding 5'-O-benzoate esters, 4b and 4d, to give 5 a and 5c, respectively. The latter, on alkaline hydrolysis, gave 2',3'-didehydro-3'-deoxy-4-thiothymidine (5b) and 2',3'-didehydro-2',3'-dideoxyuridine (5d), respectively. The same series of reactions were applied to the 5'-O-benzoate esters of 2',3'-dideoxyuridine (6a) and 3'-deoxythymidine (6b) to give 2',3'-dideoxy-4-thiouridine (7d) and 3'-deoxy-4-thiothymidine (7b), respectively. Characterization of the saturated and unsaturated thionucleosides included mass spectrometric studies. Under electron impact conditions, the thiated analogues gave more intensive parent ions than the corresponding oxygen precursors. The lipophilicity of thymidine and the 3'-deoxythymidine derivatives are enhanced significantly, as indicated, by increases in corresponding P values (1-octanol-0.1 M sodium phosphate) upon replacement of the 4-carbonyl oxygens by sulfur. Compounds 5b, 5d, 7b, and 7d were evaluated for their effects on HIV-induced cytopathogenicity of MT-2 and CEM cells. Only 5b and 7b were moderately active in protecting both cell lines against the cytolytic effect of HIV. The inhibitory effects of analogous 5b, 5d, 7b, and 7d on thymidine phosphorylation by rabbit thymus thymidine kinase were evaluated. Only 3 showed moderate affinity (K(i) = 54 μM) for the enzyme. The generally weak anti-HIV activities of the remaining thio analogues are consistent with correspondingly low susceptibilities to thymidine kinase phosphorylation as estimated from the respective K(i) values of the synthetic nucleosides. However, the phosphorylation of the 5'-monophosphate derivatives to their respective 5'-triphosphates must also be considered in connection with the weak in vitro anti-HIV effects of these thiated compounds.
STEREOSELECTIVITIES IN THE COUPLING REACTION BETWEEN SILYLATED PYRIMIDINE BASES AND 1-HALO-2,3-DIDEOXYRIBOSE
Kawakami, Hiroshi,Ebata, Takashi,Koseki, Koshi,Matsumoto, Katsuya,Matsushita, Hajime,et al.
, p. 2041 - 2054 (2007/10/02)
Coupling reactions between 1-chloro-2,3-dideoxyribose and silylated pyrimidines have been examined from the point of stereoselectivity.When the reaction was carried out in chloroform, the selectivity was in the anomeric ratio of α:β = 4:6.On the other hand, the presence of tertiary amine raises the selectivity to α:β = 3:7.
