- External transesterification of ribonucleotide esters naturally catalyzed by large ribozymes
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The intriguing chemical mechanism of the external transesterification by which large ribozymes (group I, group II, and spliceosomal introns) splice RNA has been found to operate in the methanolysis of ribonucleoside 2′-/3′-dimethyl phosphates in non-hydrogen-bonding organic solvents. Besides needing aprotic organic media this mechanism requires a high concentration of the attacking alcohol accounting for the binding of an external guanosine by group I introns and the use of a non-adjacent internal 2′-OH by group II and spliceosomal introns. This finding is the first example of an external non-ribozymic transesterification of ribonucleotide esters and the means by which this crucial biochemical reaction can be accelerated.
- Roussev, Christo D.,Ivanova, Gabriela D.,Bratovanova, Emilia K.,Vassilev, Nikolay G.,Petkov, Dimiter D.
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Read Online
- Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates
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The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.
- Ghirardello, Mattia,De Las Rivas, Matilde,Lacetera, Alessandra,Delso, Ignacio,Lira-Navarrete, Erandi,Tejero, Tomás,Martín-Santamaría, Sonsoles,Hurtado-Guerrero, Ramón,Merino, Pedro
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Read Online
- Tricyclanos: Conformationally constrained nucleoside analogues with a new heterotricycle obtained from a d-ribofuranose unit
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A novel type of nucleoside analogue in which the sugar part is replaced by a new tricycle, 3,7,10-trioxa-11-azatricyclo[5.3.1.05,11]undecane has been prepared by substrate-controlled asymmetric synthesis. 1,5-Dialdehydes obtained from properly protected or unprotected uridine, ribothymidine, cytidine, inosine, adenosine and guanosine by metaperiodate oxidation reacted readily with tris(hydroxymethyl)aminomethane to provide the corresponding tricyclic derivatives with three new stereogenic centers. Through a double cyclisation cascade process the tricyclic compounds were obtained in good to high yields, with very high diastereoselectivity. Formation of one stereoisomer, out of the eight possible, was observed in all cases. The absolute configuration of the new stereotriad-containing tricyclic systems was aided by conventional NMR experiments followed by chemical shift calculations using an X-ray crystal structure as reference that was in good agreement with H-H distances obtained from a new ROESY NMR method. The synthesis was compatible with silyl, trityl and dimethoxytrityl protecting groups. A new reagent mixture containing ZnCl2, Et3SiH and hexafluoroisopropanol was developed for detritylation of the acid-sensitive tricyclano nucleosides.
- Kicsák, Máté,Mándi, Attila,Varga, Szabolcs,Herczeg, Mihály,Batta, Gyula,Bényei, Attila,Borbás, Anikó,Herczegh, Pál
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supporting information
p. 393 - 401
(2018/02/06)
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- Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
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Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
- Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
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p. 3910 - 3917
(2017/03/27)
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- In search of flavivirus inhibitors: Evaluation of different tritylated nucleoside analogues
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Following up on a hit that was identified in a large scale cell-based antiviral screening effort, a series of triphenylmethyl alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against the dengue virus (DENV) and the yellow fever virus (YFV). Hereto, trityl moieties were attached at various positions of the sugar ring combined with subtle variations of the heterocyclic base. Several triphenylmethyl modified nucleosides were uncovered being endowed with submicromolar in vitro antiviral activity against the YFV. The most selective inhibitor in this series was 3′,5′-bis-O-tritylated-5-chlorouridine (1b) affording a selectivity index of over 90, whereas the 3′,5′-bis-O-tritylated inosine congener (5b) displayed the highest activity, but proved more toxic. The finding of these lipophilic structures being endowed with high antiviral activity for flaviviruses, should stimulate the interest for further structureeactivity research.
- Chatelain, Grégory,Debing, Yannick,De Burghgraeve, Tine,Zmurko, Joanna,Saudi, Milind,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
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p. 249 - 255
(2013/10/01)
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- Synthesis of 3′-azido-4′-ethynyl-3′,5′-dideoxy- 5′-norarabinouridine: A new anti-HIV nucleoside analogue
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3′-Azido-4′-ethynyl-3′,5′dideoxy-5′- norarabinouridine 10 was synthesized from commercial uridine 1 in which the key step is the opening of protected 2′,3′-epoxyuridine derivative 7 by sodium azide and the hydroxymethyl at 4-position of the ribose ring are replaced by ethynyl group.
- Amin, Mahmoud A.
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scheme or table
p. 1703 - 1708
(2011/04/18)
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- An efficient and selective method for the preparation of triphenylmethyl ethers of alcohols and nucleosides
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A very simple and efficient method is described for the protection of alcohols and nucleosides with benzyl monomethoxytrityl and benzyl dimethoxytrityl ethers in the presence of diethylazodicarboxylate and a catalytic amount of ceric triflate. High selectivity was observed for the tritylation of 5'-OH function of nucleosides.
- Zekri, Negar,Alamdari, Reza Fareghi
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experimental part
p. 563 - 568
(2010/08/05)
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- A solvent free and selective method for preparation of triphenylmethyl ethers of alcohols and nucleosides
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A very simple and efficient method is described for protection of alcohols and nucleosides with trityl(triphenylmethyl), mono and dimethoxytrityl chlorides in the presence of triethylamine under microwave irradiation. High selectivity was observed for tritylation of 5'-OH function of nucleosides.
- Zekri, Negar,Alamdari, Reza Fareghi,Khalafi-Nezhad, Ali
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experimental part
p. 299 - 304
(2012/04/23)
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- 3′-Bromo analogues of pyrimidine nucleosides as a new class of potent inhibitors of mycobacterium tuberculosis
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Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2′- or 3′-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3′-bromo-3′-deoxy- arabinofuranosylthymine (33) was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC 50 = 1 μg/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 μg/mL). Compound 33 also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 μg/mL concentration) than extracellular mycobacteria (75% reduction at 10 μg/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 μg/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.
- Shakya, Neeraj,Srivastav, Naveen C.,Desroches, Nancy,Agrawal, Babita,Kunimoto, Dennis Y.,Kumar, Rakesh
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experimental part
p. 4130 - 4140
(2010/09/04)
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- Novel selectivity in carbohydrate reactions, IV: DABCO-mediated regioselective primary hydroxyl protection of carbohydrates
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An efficient procedure for the regioselective tritylation of primary hydroxyl group of aldohexopyranosides and nucleosides using trityl chloride in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in dichloromethane has been developed. Subsequent acetylation of the tritylated products in the same pot has been made possible, thereby providing an efficient route to the fully protected carbohydrate derivatives that can be discriminated chemoselectively.
- Gadakh, Bharat Kacheshwar,Patil, Premanand Ramrao,Malik, Satish,Kartha, K. P. Ravindranathan
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experimental part
p. 2430 - 2438
(2009/12/03)
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- Application of ball milling technology to carbohydrate reactions: I. Regioselective primary hydroxyl protection of hexosides and nucleoside by planetary ball milling
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Dry ball milling of hexosides with trityl chloride in the presence of DABCO or Na2CO3 has been found to result in their complete conversion to the respective 6-O-trityl ethers. Further wet grinding of the reaction mixture with Ac2O in the presence of DMAP led to the respective fully protected hexosides in good to excellent yields after isolation. It has been found to be an effective one-pot two-step synthesis under solvent-free condition. The speed of homogenization has been shown to highly influence the rate and outcome of the reaction, and commercially available planetary ball mill has been proved to be very convenient for carrying out the reaction under standardized and reproducible conditions.
- Patil, Premanand Ramrao,Kartha, K.P. Ravindranathan
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p. 279 - 293
(2008/12/21)
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- Synthesis of sugar nucleotides by application of phosphoramidites
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(Chemical Equation Presented) A new method for the construction of pyrophosphates is reported based on the coupling of a sugar phosphate and a nucleoside phosphoramidite. The in situ formed phosphate-phosphite intermediate was subsequently oxidized with tBuOOH. Three UDP-N-acetylglucosamine derivatives were prepared using this one-pot procedure in good yields.
- Gold, Henrik,Van Delft, Pieter,Meeuwenoord, Nico,Codee, Jeroen D. C.,Filippov, Dmitri V.,Eggink, Gerrit,Overkleeft, Herman S.,Van Der Marel, Gijs A.
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supporting information; experimental part
p. 9458 - 9460
(2009/04/06)
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- Simultaneous removal of benzyl and benzyloxycarbonyl protective groups in 5′-O-(2-deoxy-α-D-glucopyranosyl)uridine by catalytic transfer hydrogenolysis
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Synthesis of N3,2′,3′-O-tris-(benzyloxycarbonyl)uridine and its use in the synthesis of 5′-O-(2-deoxy-α-d-glucopyranosyl)uridine is described. Simultaneous removal of benzyl and benzyloxycarbonyl groups was accomplished by catalytic transfer hydrogenolysis in the presence of Pearlman′s catalyst without competing side reactions. Copyright Taylor & Francis Group, LLC.
- Wandzik, Ilona,Bieg, Tadeusz,Kadela, Monika
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body text
p. 1250 - 1256
(2009/04/06)
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- Tetrabutylammonium bromide: An efficient media for dimethoxytritylation of the 5'-hydroxyl function of nucleosides
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An efficient procedure for selective dimethoxytritylation of the 5'-hydroxyl function of nucleosides in the presence of DABCO in molten tetrabutylammonium bromide is described. The methodology is very practical, environmentally benign and produced the desired product in less than 5 min by grinding in a hot mortar. In addition, the effects of the room temperature ionic liquid (1-butyl-3-methylimidazolium chloride) and microwave irradiation on this system were also studied and the results showed that depurination of the nucleosides occurred under microwave irradiation.
- Khalafi-Nezhad, Ali,Mokhtari, Babak
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p. 6737 - 6739
(2007/10/03)
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- A novel approach to unsaturated acyclic nucleoside analogues and the first synthesis of d4T by ring closure metathesis
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Novel unsaturated acyclic nucleoside analogues, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}uracil, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}thymine and 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}cytosine have been prepared in good yield from uridine and 5-methyluridine by periodate cleavage followed by a double Wittig reaction which introduces two vinyl groups. The thymine derivative underwent ring closure metathesis to give a novel synthesis of d4T.
- Ewing, David,Gla?on, Virginie,Mackenzie, Grahame,Postel, Denis,Len, Christophe
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p. 3503 - 3505
(2007/10/03)
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- Novel carbohydrate scaffolds. Assembly of a uridine-mannose scaffold based on tunicamycin
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A disaccharide scaffold based on tunicamycin was synthesized from D- uridine and L-mannose. The key step in disaccharide assembly was a β- mannosylation performed using Crich's modification of the sulfoxide glycosylation method. The scaffold described contains two orthogonal derivatization sites and will be used in the search for novel biologically active compounds. (C) 2000 Elsevier Science Ltd.
- Silva, Domingos J.,Sofia, Michael J.
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p. 855 - 858
(2007/10/03)
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- Preparation and cleavage reactions of 3′-thiouridylyl-(3′→5′)-uridine
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3′-Thiouridylyl-(3′→5′)-uridine [(Us)pU] 3 is prepared by coupling together the disulfide 14 and the 5′-H-phosphonate 18, and then removing the protecting groups. (Us)pU 3 readily undergoes cleavage in 0.05 mol dm-3 sodium glycinate buffer (pH 10.06) at 50 °C to give, in the first instance, uridine 4 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21; in glacial acetic acid at 30 °C, it rapidly undergoes cleavage in essentially the same way. The behaviour of (Us)pU 3 is compared with that of uridylyl-(3′→5′)-uridine (UPU) 1a under the same basic and acidic reaction conditions. (Us)pU 3 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21 are both substrates for ribonuclease A; (Us)pU 3 is a substrate for Crotalus adamanteus snake venom phosphodiesterase but not for calf spleen phosphodiesterase.
- Liu, Xiaohai,Reese, Colin B.
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p. 2227 - 2236
(2007/10/03)
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- Uracil- and thymine-substituted thymidine and uridine derivatives
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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
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p. 1835 - 1838
(2007/10/03)
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- Synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine; A unique antiviral nucleoside
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The synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine 1 was accomplished using two different approaches. First, uridine and cytidine were used to prepare the key intermediate epoxides 15 and 31 which were opened with cyanide, deoxygenated by elimination to vinyl nitriles 17 and 36, and reduced by 1,4 hydride addition to the saturated nitriles 18 and 37. Secondly, a novel Rh-catalyzed hydroformylation reaction of 2',3'-didehydro-2',3'-dideoxycytidine 46 was used to prepare 1 in four steps. The attempted use of 2'-deoxyuridine and 2'-deoxycytidine to prepare 1 is also discussed.
- Faul, Margaret M.,Huff, Bret E.,Dunlap, Steven E.,Frank, Scott A.,Fritz, James E.,Kaldor, Stephen W.,LeTourneau, Michael E.,Staszak, Michael A.,Ward, Jeffrey A.,Werner, John A.,Winneroski, Leonard L.
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p. 8085 - 8104
(2007/10/03)
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- Synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides by reaction of 5′-protected nucleoside 2′,3′-dimesylates with telluride dianion: A general route from cis vicinal diols to olefins
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2′,3′-Dimesylates of 5′-protected nucleosides are converted into the corresponding 2′,3′-didehydro2′,3′-dideoxy compounds by treatment with telluride dianion in the form of the sodium or lithium salt. The method is well-suited to the preparation of unsaturated nucleosides that can be converted into compounds that are believed to be useful in the treatment of AIDS. The deoxygenation is general for vicinal dimesylates that have, or may adopt, a synperiplanar conformation. With straight chain compounds the reaction is stereospecific. In some cases, similar, but slower, deoxygenations can be performed with selenide dianion.
- Clive, Derrick L. J.,Wickens, Philip L.,Sgarbi, Paulo W. M.
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p. 7426 - 7437
(2007/10/03)
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- Stereospecific synthesis and anti-HIV activity of (Z)2'- and (E)3'- deoxy-2'(3')-C-(chloromethylene) pyrimidine nucleosides
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Reaction of 1-[2,5(and 3,5)-di-O-trityl-β-D-erythro-pentofuran-3(and 2)- ulosyl]uracil derivatives 5 and 6 with (chloromethyl)triphenylphosphorane resulted in the stereoselective formation of (E)-3'- and (Z)-2'- chloromethylene derivatives 7 (69%) and 8 (53%), respectively, deprotection of which gave 9 and 10. Transformation of the uracil nucleoside 7 into cytosine one followed by deprotection yielded 12. The latter was convened into the arabinoside 14. The fully deprotected chloromethylene nucleosides were tested for their activity against HIV-1 and HIV-2.
- Kalinichenko,Rubinova,Borisov,Balzarini,De Clercq,Mikhailopulo
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p. 533 - 536
(2007/10/02)
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- Nucleosides. LVI. Synthesis and chemical modifications of 3'-deoxy- pyrimidine nucleosides
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3'-Deoxyuridine(1) and 3'-deoxycytidine(2) were prepared with improved yields by two different methods applying either the Barton procedure to appropriate 2',5'-di-O-protected pyrimidine nucleosides or by choosing the direct glycosylation of the pyrimidine bases with 1,2-di-O-acetyl-5-O- toluoyl-3-deoxy-D-erythro-pentofuranose via the silylation approach. Suitable protecting groups for the sugar moiety have been found in the trityl, tert- butyldimethylsilyl and the thexyl groups which are inert in the radical deoxygenation process. The newly synthesised compounds were characterized by elemental analyses and UV and 1H-NMR spectra.
- Rhie,Pfleiderer
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p. 1425 - 1452
(2007/10/02)
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- Synthesis of 2',3'-Dithiouridine
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The synthesis of 2',3'-dithiouridine 2, starting from uridine, is described.
- Johnson, Richard,Joshi, Bhalchandra V.,Reese, Colin B.
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p. 133 - 134
(2007/10/02)
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- Phosphotriesters Approach to the Synthesis of Oligonucleotides: A Reappraisal
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The phosphotriester approach to the synthesis of oligodeoxyribo- and oligoribo-nucleotides in solution has been reinvestigated.The efficacy of mesitylene-2-sulfonyl chloride (MSCl) 15a, 2,4,6-triisopropylbenzenesulfonyl chloride (TrisCl) 15b, 4-bromobenzenesulfonyl chloride 15c, naphthalene-1-sulfonyl chloride 39, and 2- and 4-nitrobenzenesulfonyl chlorides 40a and 40b, respectively, as activating agents has been examined.The latter arenesulfonyl chlorides have been used in conjunction with the following nucleophilic catalysts: 1-methylimidazole, 3-nitro-1H-1,2,4-triazole 19, 5-(3-nitrophenyl)-1H-tetrazole 20a, 5-(3,5-dinitrophenyl)-1H-tetrazole 20b, 5-(1-methylimidazol-2-yl)-1H-tetrazole 21, 5--1H-tetrazole 22, 4-ethoxypyridine 1-oxide 14a, 4,6-dinitro-1-hydroxybenzotriazole 29a, 1-hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole 29b, 1-hydroxy-5-phenyltetrazole 30a and 1-hydroxy-5-(3-nitrophenyl)tetrazole 30b.The rates of formation and yields of the fully protected dideoxyribonucleoside and diribonucleoside phosphates 37 and 47, respectively, were determined using various combinations of activating agents and nucleophilic catalysts.Although 2- and 4-nitrobenzenesulfonyl chlorides 40a and 40b, respectively, proved to be the most powerful activating agents, their use in the deoxy-series led to the formation of by-products and hence to unsatisfactory isolated yields of the dideoxyribonucleoside phosphate 37.
- Reese, Colin B.,Pei-Zhuo, Zhang
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p. 2291 - 2302
(2007/10/02)
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- Regioselective Transformations of 2',3'-Seconucleosides into Anhydro Structures and Chiral Crown Ethers
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Intramolecular cyclisation of properly protected and activated derivatives of 2',3'-secouridine (= 1--ethyl>uracil; 1) provided access to the 2,2'-, 2,3'-, 2,5'-, 2',5'-, 3',5'-, and 2',3-anhydro-2',3'-secouridines 5, 16, 17, 26, 28 and 31, respectively (Schemes 1-3).Reaction of 2',5'-anhydro-3'-O-(methylsulfonyl)- (25) and 2',3'-anhydro-5'-O-(methylsulfonyl)-2',3'-secouridine (32) with CH2Cl2 in the presence of 1,8-diazabicycloundec-7-ene generated the N(3)-methylene-bridged bis-uridine structure 37 and 36, respectively (Scheme 3).Novel chiral 18-crown-6 ethers 40 and 44, containing a hydroxymethyl and a uracil-1-yl or adenin-9-yl as the pendant groups in a 1,3-cis relationship, were synthesized from 5'-O-(triphenylmethyl)-2',3'-secouridine (2) and 5'-O,N6-bis(triphenylmethyl)-2',3'-secoadenosine (41) on reaction with 3,6,9-trioxaundecane-1,11-diyl bis(4-toluenesulfonate) and detritylation of the thus obtained (triphenylmethoxy)methyl compound 39 and 43, respectively (Scheme 4).
- Skaric, Vinko,Caplar, Vesna,Skaric, Durdica,Zinic, Mladen
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p. 493 - 506
(2007/10/02)
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- SYNTHESIS AND TRANSFORMATION OF DERIVATIVES OF THE N- AND O-GLYCOSIDES OF D-RIBOFURANOIC ACID
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A method was developed for the nonselective oxidation of pyrimidine nucleosides and methyl β-D-ribofuranoside to the uronic acids by successive treatment first with triphenylchloromethane and then with acetic anydride in pyridine, followed by oxidation with chromic anhydride in acetone in the presence of sulfuric acid.The transformations of the obtained uronic acids into anhydronucleosides by the action of phthalimide and into 3',4'-unsaturated nucleosides by the action of 1,5-diazabicycloundec-5-ene are described.
- Timoshchuk, V. A.
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p. 1198 - 1204
(2007/10/02)
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- Azide- Or fluorine-containing 2′ & 3′-azolyluridines by regioselective opening of 1-(2′,3′-anhydro-β-d-lyxofuranosyl)uracils
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Azide- or fluorine-containing imidazol-1-yl, pyrazol-1-yl, and 1,2,4-triazol-1-yl 2′,3′-dideoxyuridines have been synthesized from uridine in 5-6 steps, via 2′,3′-β-cpoxy ? derivatives. Regioselective oxirane-ring openings have been accomplished by appropriate choice of the reactions conditions.
- Ariza, Xavier,Garces, Josep,Vilarrasa, Jaume
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p. 4069 - 4072
(2007/10/02)
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- Synthesis and Anticancer Activity of Various 3'-Deoxy Pyrimidine Nucleoside Analogues and Crystal Structure of 1-(3-Deoxy-β-D-threo-pentofuranosyl)cytosine
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Various 3'-deoxy pyrimidine nucleoside analogues have been synthesized for evaluation as potential anticancer and antiviral agents.Among these compounds, 1-(3-deoxy-β-D-threo-pentofuranosyl)cytosine (10, 3'-deoxy-ara-C) and 3'-deoxycytidine (22) had significant anticancer activity against CCRF-CEM, L1210, P388, and S-180 cancer cell lines in vitro, producing ED50 values of 2,10,5,and 34 μM, respectively, for 3'-deoxy-ara-C (10); and 25, 5, 2.5, and 15μM, respectively, for 3'-deoxycytidine (22).Thus, 3'-deoxy-ara-C (10) was 12.5 times more active against CCRF-CEM cells than 3'-deoxycytidine (22).The 2'-O-acetyl, 5'-O-acetyl, and 2',5'-di-O-acetyl derivatives of 3'-derivatives of 3'-deoxy-ara-C (10), compounds 34, 31, and 30, demonstrated anticancer activity in the same range as 3'-deoxy-ara-C (10) against CCRF-CEM, L1210, P388, and S-180 cells.The 5'-O-acetyl derivative (31) had significantly greater activity against CCRF-CEM with an ED50 value of 0.4 but this compound also showed similar activity, as did 3'-deoxy-ara-C against L1210, P388, and S-180 with ED50 values of 3, 3, and 13 μM, respectively. 3'-Deoxy-ara-C was also evaluated in vitro against HSV-2, HCMV, and GPCMV viruses and was found to be not very active with respective IC50 values of 110, 220, and 1000 μM.The single-crystal structure of 3'-deoxy-ara-C (10) was determined by X-ray crystallography.There are two molecules of the nucleoside and one molecule of water in the asymmetric unit.The sugar moieties of two nucleoside molecules adopt different conformations.In molecule A, the ring pucker is C3'-endo with P=18.7 deg and τm= 37.3 deg, while the CH2OH side chain is gauche+.In molecule B, the ring pucker is C2'-endo with P= 156.8 deg and τm = 37.8 deg and the side chain is trans.
- Lin, Tai-Shun,Yang, Jin-Hua,Liu, Mao-Chin,Shen, Zhi-Yi,Cheng, Yung-Chi,et al.
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p. 693 - 701
(2007/10/02)
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- SYNTHESIS AND CHARACTERIZATION OF 4-DIMETHYLAMINO-N-TRIPHENYLMETHYLPYRIDINIUM CHLORIDE, A POSTULATED INTERMEDIATE IN THE TRITYLATION OF ALCOHOLS
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4-Dimethylamino-N-triphenylpyridinium chloride (1) reacts with primary but not secondary alcohols to produce trityl ethers in good yield; in addition, amines may be selectively N-tritylated with 1 in the presence of alcohols.
- Hernandez, O.,Chaudhary, S. K.,Cox, R. H.,Porter, J.
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p. 1491 - 1494
(2007/10/02)
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