Free accessResearch articleFirst published online 2005-12
Synthesis and Antiviral Activities of 1,2,3-triazole Functionalized Thymidines: 1,3-dipolar Cycloaddition for Efficient Regioselective Diversity Generation
Efficient regioselective synthesis of nucleoside conjugates was achieved by cycloaddition reaction of azides and alkynes using sodium ascorbate/CuSO4 system as a catalyst. These 16 novel thymidine analogues were obtained in excellent yields (75–100%), employing mild reaction conditions with a broad scope of structural modification. For the compounds tested, no specific antiviral effects could be witnessed against a broad range of viruses.
AlvarezRVelazquezSSan-FelixAAquaroSDe ClercqEPernoCFKarlssonABalzariniJ & CamarasaM (1994) 1,2,3-Triazole-[2,5-bis-0-(tert-butyldimethylsilyl)- (beta)-d-ribofuranosyl]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole 2″,2″-dioxide) (TSAO) analogs: Synthesis and anti-HIV-1 activity J. Journal of Medicinal Chemistry37: 4185–4194.
2.
BalzariniJNaesensLSlachmuyldersJNiphuisHRosenbergIHolýASchellekensH & De ClercqE (1991) 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) effectively inhibits Simian immunodeficiency virus (SIV) infection in Rhesus monkeys. AIDS5: 21–28.
3.
BehshadEParkinSE & BollingerJM (2004) Mechanism of cysteine desulfurase Slr0387 from synechocystis sp. PCC 6803: Kinetic analysis of cleavage of the persulfide intermediate by chemical reductants. Biochemistry43: 12 220–12 226.
4.
BreslowR (2004) Determining the geometries of transition states by use of antihydrophobic additives in water. Accounts of Chemical Research37: 471–486.
5.
BrzozowskiZ (1998) 2-Mercapto N-(azolyl)benzenesulfonamides. VI. Synthesis and anti-HIV activity of some new 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives containing the 1,2,4-triazole moiety fused with a variety of heteroaromatic rings. Acta Poloniae Pharmaceutica55: 473–480.
6.
BurnsJAButlerJCMoranJ & WhitesidesGM (1991) Selective reduction of disulfides by tris(2-carboxyethyl)phosphine. The Journal of Organic Chemistry56: 2648–2650.
7.
DaviesMB (1992) Reactions of L-ascorbic acid with transition metal complexes. Ployhedron11: 285–321.
8.
De ClercqEDescampsJVerhelstGWalkerRTJonesASTorrencePF & ShugarD (1980). Comparative efficacy of different antiherpes drugs against different strains of herpes simplex virus. Journal of Infectious Diseases141: 563–574.
9.
De ClercqEHolýARosenbergISakumaTBalzariniJ & MaudgalPC (1986). A novel selective broad-spectrum anti-DNA virus agent. Nature323: 464–467.
10.
DeitersACroppTAMukherjiMChinJWAndersonJC & SchultzPG (2003) Adding amino acids with novel reactivity to the genetic code of Saccharomyces cerevisiae. Journal of the American Chemical Society125: 11 782–11 783.
11.
FanW-Q & KatritzkyA (1996) 1,2,3-triazoles. In Comprehensive Heterocyclic Chemistry II, Vol 4; pp. 1–10. Edited by StorrRC and KatrizkyARRessCW & ScrivenEFV. Oxford: Pergamon.
12.
FaucherA-M & Grand-MaitreC (2003) tris(2-Carboxyethyl)phosphine (TCEP) for the reduction of sulfoxides, sulfonylchlorides, N-oxides, and azides. Synthetic Communications33: 3503–3511.
13.
FinleyKT (1980) Triazoles-1,2,3. In The Chemistry of Heterocyclic Compounds, vol. 39; pp. 1–347. Edited by MontgomeryJA. New York: John Wiley & Sons.
14.
HäbichDBarthW & RösnerM (1989) Synthesis of 3′-(1,2,3-triazol-1-yl)-3′-deoxythymidines. Heterocycle29: 2083–2087.
15.
HimoFLovellTHilgrafRRostovtsevVVNoodlemanLSharplessKB & FokinVV (2005) Journal of the American Chemical Society127: 210–216.
16.
HorwitzJPTomsonAJUrbanskiJA & ChuaJ (1962) Nucleosides. I. 5′-Amino-5′-deoxyuridine and 5′-amino-5′-deoxythymidine. The Journal of Organic Chemistry27: 3045–3048.
17.
HuisgenR (1984) 1,3-Dipolar cycloadditions — Introduction, survey, mechanism. In 1,3-Dipolar Cycloaddition Chemistry; pp. 1–176. Edited by PadwaA. New York: Wiley.
18.
LewisWGGreenLGGrynszpanFRadicZCarlierPRTaylorPFinnGM & SharplessKB (2002) Click chemistry in situ: Acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angewandte Chemie-Internaional Edition in English41: 1053–1057.
19.
LinH & WalshCT (2004) A chemoenzymatic approach to glycopeptide antibiotics. Journal of the American Chemical Society126: 13 998–14 003.
20.
LinkAJ & TirrellDA (2003) Cell surface labeling of Escherichia coli via copper(I)-catalyzed [3+2] cycloaddition. Journal of the American Chemical Society125: 11 164–11 165.
21.
LinTS & PrusoffWH (1978) Synthesis and biological activity of several amino analogs of thymidine. Journal of Medicinal Chemistry21: 109–112.
22.
ManetschRKrasińskiARadićZRaushelJTaylorPSharplessKB & KolbHC (2004) In situ click chemistry: Enzyme inhibitors made to their own specifications. Journal of the American Chemical Society126: 12 809–12 818.
23.
RideoutDC & BreslowR (1980) Hydrophobic acceleration of Diels-Alder reactions. Journal of the American Chemical Society102: 7816–7817.
24.
RileyTALarsonSBAveryTLFinchRA & RobinsRK (1990) 1,2,4-Diazaphosphole nucleosides. Synthesis, structure, and antitumor activity of nucleosides with a .lambda.3 phosphorus atom. Journal of Medicinal Chemistry33: 572–576.
25.
RosowskyARuprechtRM & SolunVC (1989) Synthesis of 3′-O-propargylthymidine as a candidate antiretroviral agent. Nucleosides & Nucleotides8: 491–497.
26.
RostovtsevVVGreenLGFokinVV & SharplessKB (2002) A stepwise huisgen cycloaddition process: Copper(I)-catalyzed regioselective ‘ligation’ of azides and terminal alkynes. Angewandte Chemie-Internaional Edition in English41: 2596–2599.
27.
StetsenkoDA & GaitMJ (2000) Efficient conjugation of peptides to oligonucleotides by ‘native ligation’. The Journal of Organic Chemistry65: 4900–4908.
28.
TornøeCWChristensenC & MeldalM (2002) Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. The Journal of Organic Chemistry67: 3057–3064.
29.
TourirteMOulihTLazrekHBBarascutJLImbachJL & AlmasoudiNA (2003) Synthesis of 3′-deoxy-3′-[4-(pyrimidin-1-yl) methyl-1,2,3-triazol-1-yl]thymidine via 1,3-dipolar cycloaddition. Nucleosides, Nucleotides & Nucleic Acids22: 1985–1993.
30.
WangQChanTRHilgrafRFokinVVSharplessKB & FinnMG (2003) Bioconjugation by copper(I)-catalyzed azide-alkyne [3+2] cycloaddition. Journal of the American Chemical Society125: 3192–3193.
31.
WangPHolleckerLPankiewiczKWPattersonSEWhitakerTMcBrayerTRTharnishPMSidwellRWStuyverLJOttoMJSchinaziRF & WatanabeKA (2004) Synthesis of N3,5′-cyclo-4-(β-d-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one, a novel compound with anti-hepatitis C virus activity. Journal of Medicinal Chemistry47: 6100–6103.
32.
WangZ-X & QinH-L (2003) Regioselective synthesis of 1,2,3-triazole derivatives via 1,3-dipolar cycloaddition reactions in water. Chemical Communication19: 2450–2451.
33.
WigerinckPVan AerschotAClaesPBalzariniJDe ClercqE & HerdewijnP (1989) 3′-(1,2,3-Triazol-1-yl)-2′,3′-dideoxythymidine and 3′-(1,2,3-triazol-1-yl)-2′,3′-dideoxyuridine. Journal of Heterocycle Chemistry26: 1635–1642.