- A new reagent for the formation of anhydronucleosides
-
5'-O-Trityl-thymidine reacts with excess perfluorobutanesulfonyl fluoride/DBU in toluene to 5'-O-trityl-2,3'-anhydrothymidine in 75% yield. Free thymidine gives rise to 4',5'-dehydro-2,3'-anhydrothymidine and to 5'-fluoro-2,3'-anhydrothymidine.
- Bennua-Skalmowski,Vorbrueggen
-
-
Read Online
- Intermediate preparation zidovudines and method
-
Disclosed is a method for preparing zidovudine (B). The method comprises the following steps: 1) 2'-halothymidine (A) is used as the raw material to obtain a compound of formula (I) by protecting the hydroxyl group thereof in the 5'-position; 2) the compound of formula (I) is subjected to the acylation of the hydroxyl group in the 3'-position to obtain a compound of formula (VI); 3) the compound of formula (VI) is dehalogenated to obtain a compound of formula (111); 4) the compound of formula (III) is subjected to an elimination reaction to obtain a compound of formula (IV); 5) the compound of formula (IV) is subjected to an azidation reaction to obtain a compound of formula (V); and 6) the compound of formula (V) is deprotected to obtain zidovudine (B); the specific reaction formula being shown in (C)below. In the formulae: X is a halogen, P1 is a protecting group for hydroxyl; and P2 is C1-C4 alkylsulfonyl, fluoro-C1-C4 alkylsulfonyl, arylsulfonyl or -CS-R, wherein R is C1-C4 alkyl.
- -
-
-
- Synthesis, structure, and biological evaluation of C-2 sulfonamido pyrimidine nucleosides
-
The C-2 sulfonamido pyrimidine nucleosides were prepared by opening the 2,2′- or 2,3′-bond in anhydronucleosides under nucleophilic attack of sulfonamide anions. Reaction of the sodium salt of p-toluenesulfonamide or 2-(aminosulfonyl)-N,N-dimethylnicotinamide with 2,2′-anhydro-1-(β-D-arabinofuranosyl)cytosine gave the C-2 sulfonamido derivatives in excellent yields. Ring opening of the less reactive 2,2′-anhydrouridine and 2,3′-anhydrothymidine could be accomplished with DBU/CH3CN activation of p-toluenesulfonamide, giving moderate yields for C-2 sulfonamido derivatives. The action of acetic acid or ZnBr2/CH2Cl2 on 5-methyl-N2-tosyl-1-(2-deoxy-5-O-trityl-β-D-threo- pentofuranosyl)isocytosine led to the cleavage of both the protection group and the nucleoside bond, yielding 5-methyl-N2-tosylisocytosine as the major product. Structures of the prepared C-2 sulfonamido nucleosides were confirmed by the 1D and 2D NMR experiments, and X-ray structural analysis of 4-imino-N2-tosylamino-1-(β-D-arabinofuranosyl)pyrimidine. Both methods confirmed β-configuration and anti-conformation of the 2-sulfonamido nucleosides. The investigated compounds displayed moderate inhibition of tumor cell growth in vitro, as determined by the MTT assay using six different human tumor cell lines.
- Krizmani?, Irena,Vi?njevac, Aleksandar,Lui?, Marija,Glava?-Obrovac, Ljubica,?ini?, Mladen,?ini?, Biserka
-
p. 4047 - 4057
(2007/10/03)
-
- Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase
-
A number of 2′- and 3′-modified thymidine 5′-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2′-halogeno substituent and a 3′-azido function are the most favorable leads for further development of potent inhibitors of this enzyme.
- Vanheusden, Veerle,Munier-Lehmann, Helene,Pochet, Sylvie,Herdewijn, Piet,Van Calenbergh, Serge
-
p. 2695 - 2698
(2007/10/03)
-
- A facile one-pot synthesis of 2,3'-anhydro-2'-deoxyuridines via 3'-O-imidazolylsulfonates
-
Continued interests in the novel synthetic methods of the pivotal compound, 2,3'-anhydro-2'-deoxyribonucleosides (7) uncovered a facile one-pot conversion of 5 with 1,1'-sulfonyldiimidazole in basic conditions to 7 with almost quantitative yields (91-99%).
- No,Dong Seong Shin,Bok Ju Song,Ahn,Ha
-
p. 3873 - 3882
(2007/10/03)
-
- Nucleophilic N1→N3 rearrangement of 5′-O-trityl-O2,3′-cycloanhydrothymidine
-
5′-O-Trityl-O2,3′-cycloanhydrothymidine (1) heated at 150°C in the presence of O,O-diethyl phosphate or O,O-diethyl phosphorothioate anions undergoes rearrangement into N3-isomer (2); its structure was established by both advanced NMR methods and X-ray crystallographic studies. The most probable mechanism of 1 → 2 rearrangement relies upon reversibility of glycosidic bond cleavage process.
- Yang, Xian-Bin,Misiura, Konrad,Stec, Wojciech J.,Potrzebowski, Marek J.,Kazmierski, Slawomir,Wieczorek, Michal,Majzner, Wieslaw R.,Bujacz, Grzegorz D.
-
p. 1657 - 1673
(2007/10/03)
-
- Uracil- and thymine-substituted thymidine and uridine derivatives
-
The four possible 3'-uracil-1-yl and 3'-thymin-1-yl derivatives of 3'- deoxythymidine and the four analogous derivatives of 2'-deoxyuridine have been synthesised from thymidine and uridine, respectively. Advantages of the 2-(methoxycarbonyl)vinyl group to prevent the formation of anhydronucleosides and SnCl2/PhSH/Et3N in relation to H2/Pd for the reduction of most azido groups are disclosed.
- Costa, Anna M.,Faja, Montserrat,Farras, Jaume,Vilarrasa, Jaume
-
p. 1835 - 1838
(2007/10/03)
-
- Darstellung und Charakterisierung von Trifluormethylchalkogenyl substituierten Nucleosiden
-
5-Trifluoromethylchalcogenyl-substituted 2'-desoxy-uridines and -cytidines have been synthesized from 2-desoxy-3,5-di-O-(4-methylbenzoyl)-α-D-ribofuranosyl chloride and CF3E-substituted (E=S, SO2, Se) silylated pyrimidines by a modified Hilbert-Johnson reaction.By choosing proper reaction conditions β-anomers may be obtained as the main product.The nucleoside are deprotected by basic transesterification with NH3/CH3OH.After recrystallization from H2O/C2H5OH, 5-trifluoromethylchalcogenyl-2'-desoxynucleosides are formed in good yields.Systematically studiedsubstitution reactions on 5-trifluoromethylsulfanyl-2'-desoxyuridine are described. 5-Trifluoromethylsulfanyl-2',3'-didesoxyuridine is formed by Barton desoxygenation.For the first time, CF3S substitutions at the sugar part of a nucleoside are described.
- Haas, Alois,Lieb, Max,Steffens, Bernd
-
-
- Synthesis and biological activity of 3'-azido- and 3'-amino substituted nucleoside analogs
-
The product distribution obtained in the reaction of 1-(5-0-trityl-0-mesyl-2-deoxy-β-D-erythro-pentofuranosyl)-2,4-(1H, 3H)-pyrimidinedione with lithium azide in N, N'-dimethylformamide at 100°C depends on the nature of the substituent in 5. The results may be explained by a difference in the acidity of the pyrimidinedione. The reaction of the more acidic nucleosides (X = I, F) appears to proceed preferentially through the 2,3'-anhydro intermediate, whereas for the less acidic products (X = H, CH3) direct nucleophilic displacement by the azide ion predominates. The different 3'-azidfo derivatives were reduced to 3'-amino compounds. All 3'-azido- and 3'-aminopyrimidine nucleosides were tested against herpes simplex virus, vaccinia and vesicular stomatitis virus and on murine L1210 cell growth. None of the substances exhibited significant activity.
- Colla,Herdewijn,De Clercq,et al.
-
p. 295 - 301
(2007/10/02)
-
- One-Step Synthesis of 5'-Azido-nucleosides
-
Regioselective azidation of unprotected or appropriately protected nucleosides was conducted by means of the reagent triphenylphosphine-carbon tetrabromide-lithium azide.By use of this reagent, 5'-azido-5'-deoxynucleosides were prepared conveniently in one step from nucleosides in high yields.Secondary hydroxy-groups of appropriately 5'-protected nucleosides were also converted by the reagent to azido-functions with complete inversion.
- Yamamoto, Isamu,Sekine, Mitsuo,Hata, Tsujiaki
-
p. 306 - 310
(2007/10/02)
-