Improved microwave-assisted ligand-free Suzuki–Miyaura cross-coupling of 5-iodo-2′-deoxyuridine in pure water

A facile and efficient methodology for direct synthesis of 5-aryl-2′-deoxyuridines was developed through ligand-free Suzuki–Miyaura cross-coupling reactions starting from totally deprotected 5-iodo-2′-deoxyuridine and various boronic acids. Reactions were performed, in pure water, in the presence of very low loading of palladium either by classical thermal heating or with the assistance of microwave irradiation yielding 5-arylated uridine derivatives in moderate to good yields within short reaction times.

[1]  R. Huber,et al.  Pyrene as a fluorescent probe for DNA base radicals. , 2003, Chemical communications.

[2]  Clemens Wagner,et al.  Reductive electron transfer in phenothiazine-modified DNA is dependent on the base sequence. , 2005, Chemistry.

[3]  P. Čapek,et al.  Cross-coupling reactions of unprotected halopurine bases, nucleosides, nucleotides and nucleoside triphosphates with 4-boronophenylalanine in water. Synthesis of (purin-8-yl)- and (purin-6-yl)phenylalanines. , 2006, Organic & biomolecular chemistry.

[4]  N. Leadbeater,et al.  Rapid and amenable suzuki coupling reaction in water using microwave and conventional heating. , 2003, The Journal of organic chemistry.

[5]  Angel Díaz-Ortiz,et al.  Microwaves in organic synthesis. Thermal and non-thermal microwave effects. , 2005, Chemical Society reviews.

[6]  T. Fiebig,et al.  Electron injection into DNA: synthesis and spectroscopic properties of pyrenyl-modified oligonucleotides. , 2002, Chemistry.

[7]  R. Pohl,et al.  Synthesis and photophysical properties of biaryl-substituted nucleos(t)ides. Polymerase synthesis of DNA probes bearing solvatochromic and pH-sensitive dual fluorescent and 19F NMR labels. , 2012, The Journal of organic chemistry.

[8]  Joshua M. Sadler,et al.  "Reverse fleximers": introduction of a series of 5-substituted carbocyclic uridine analogues. , 2008, Nucleic acids symposium series.

[9]  E. Clercq.  Strategies in the design of antiviral drugs , 2010, Nature Reviews Drug Discovery.

[10]  H. Wagenknecht,et al.  Synthesis of 5‐(2‐Pyrenyl)‐2′‐deoxyuridine as a DNA Modification for Electron‐Transfer Studies: The Critical Role of the Position of the Chromophore Attachment , 2008 .

[11]  Marc Delarue,et al.  Enzymatic and Structural Analysis of Inhibitors Designed against Mycobacterium tuberculosis Thymidylate Kinase , 2003, The Journal of Biological Chemistry.

[12]  N. Leadbeater,et al.  Ligand-free palladium catalysis of the Suzuki reaction in water using microwave heating. , 2002, Organic letters.

[13]  W. Dehaen,et al.  Microwave-enhanced synthesis of N-shifted buflavine analogues via a Suzuki-ring-closing metathesis protocol. , 2005, Organic letters.

[14]  C. Len,et al.  Synthesis of 2',3'-didehydro-2',3'-dideoxynucleosides having variations at either or both of the 2'- and 3'-positions , 2006 .

[15]  T. Cihlar,et al.  Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. , 2010, Antiviral research.

[16]  R. Pohl,et al.  Switching the Regioselectivity of Direct C–H Arylation of 1,3‐Dimethyluracil , 2009 .

[17]  Jieping Zhu,et al.  Microwave-assisted intramolecular Suzuki-Miyaura reaction to macrocycle, a concise asymmetric total synthesis of biphenomycin B. , 2005, Organic letters.

[18]  R. Pohl,et al.  6-(Het)aryl-7-deazapurine ribonucleosides as novel potent cytostatic agents. , 2010, Journal of medicinal chemistry.

[19]  Tony Taldone,et al.  Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines. , 2009, Bioorganic & medicinal chemistry letters.

[20]  N. Kuhnert.  Microwave-assisted reactions in organic synthesis--are there any nonthermal microwave effects? , 2002, Angewandte Chemie.

[21]  N. Leadbeater,et al.  Open-Vessel Microwave-Promoted Suzuki Reactions Using Low Levels of Palladium Catalyst: Optimization and Scale-Up , 2006 .

[22]  F. Wüst,et al.  No‐carrier added synthesis of 18F‐labelled nucleosides using Stille cross‐coupling reactions with 4‐[18F]fluoroiodobenzene , 2004 .

[23]  A. Loupy,et al.  A tentative rationalization of microwave effects in organic synthesis according to the reaction medium, and mechanistic considerations , 2001 .

[24]  Tun-Cheng Chien,et al.  Practical synthesis of 6-aryluridines via palladium(II) acetate catalyzed Suzuki–Miyaura cross-coupling reaction , 2011 .

[25]  G. Wagner,et al.  A facile two-step synthesis of 8-arylated guanosine mono- and triphosphates (8-aryl GXPs). , 2006, Organic & biomolecular chemistry.

[26]  K. Dawood.  Microwave-assisted Suzuki–Miyaura and Heck–Mizoroki cross-coupling reactions of aryl chlorides and bromides in water using stable benzothiazole-based palladium(II) precatalysts , 2007 .

[27]  S. El Kazzouli,et al.  Supported Synthesis and Functionnalization of 2″-Deoxyuridine by Suzuki-Miyaura Cross-Coupling , 2007, Nucleosides, Nucleotides & Nucleic Acids.

[28]  E. Clercq,et al.  In search of a selective therapy of viral infections. , 2010, Antiviral research.

[29]  P. Gannett,et al.  Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts. , 2003, The Journal of organic chemistry.

[30]  W. Dehaen,et al.  Microwave-assisted transition-metal-catalyzed synthesis of N-shifted and ring-expanded buflavine analogues. , 2007, Chemistry.

[31]  C. Len,et al.  Nucleoside Analogues with a Novel Glycone Based on the Benzo[C]Furan Core , 1999 .

[32]  B. Fischer,et al.  Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties. , 2012, Organic & biomolecular chemistry.

[33]  Mitsunobu Nakamura,et al.  Syntheses and fluorescence of RNA conjugates having pyrene-modified adenosine and nitrobenzene-modified uridine base pairs , 2010 .

[34]  C. Len,et al.  Electrospray tandem mass-spectrometric analysis of diastereo- and stereoisomeric pyrimidine nucleoside analogues based on the 1,3-dihydrobenzo[c]furan core. , 2003, Carbohydrate research.

[35]  H. Wagenknecht,et al.  Preparation of Pyrenyl-Modified Nucleosides via Suzuki-Miyaura Cross-Coupling Reactions , 2002 .

[36]  E. Clercq,et al.  Antiviral drug discovery and development: where chemistry meets with biomedicine. , 2005, Antiviral research.

[37]  H. Kumamoto,et al.  A versatile intermediate for the synthesis of 3′-substituted 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A): preparation of 3′-C-stannyl-d4A via radical-mediated desulfonylative stannylation , 2002 .

[38]  C. Len,et al.  Facile separation of chiral 1,3-dihydrobenzo[c]furan derivatives using a d-xylose moiety as a protecting group , 2000 .

[39]  D. Villemin,et al.  Palladium-catalysed phenylation of heteroaromatics in water or methylformamide under microwave irradiation , 2001 .

[40]  J. Neyts,et al.  Synthesis of 5-aryltriazole ribonucleosides via Suzuki coupling and promoted by microwave irradiation , 2006 .

[41]  S. Islam,et al.  Convenient Synthesis of 5‐Aryl Uracils , 2007 .

[42]  L. Agrofoglio,et al.  Efficient Synthesis of Unprotected C-5-Aryl/Heteroaryl-2'-deoxyuridine via a Suzuki-Miyaura Reaction in Aqueous Media , 2012, Molecules.

[43]  B. Froehler,et al.  5-Heteroaryl-2'-deoxyuridine Analogs. Synthesis and Incorporation into High-Affinity Oligonucleotides , 1994 .

[44]  R. Pohl,et al.  Regioselective direct C-H arylations of protected uracils. Synthesis of 5- and 6-aryluracil bases. , 2011, The Journal of organic chemistry.

[45]  R. Benhida,et al.  Synthesis and in vitro antileishmanial activity of 5-substituted-2'-deoxyuridine derivatives. , 2005, Bioorganic chemistry.

[46]  P. Guenot,et al.  Palladium-catalyzed synthesis of uridines on polystyrene-based solid supports. , 2004, Journal of combinatorial chemistry.

[47]  G. Crisp,et al.  Palladium-catalysed coupling of uridine triflate with organostannanes. , 1990 .

[48]  G. Quéléver,et al.  Direct synthesis of 5-aryltriazole acyclonucleosides via Suzuki coupling in aqueous solution , 2007 .

[49]  P. Čapek,et al.  An efficient method for the construction of functionalized DNA bearing amino acid groups through cross-coupling reactions of nucleoside triphosphates followed by primer extension or PCR. , 2007, Chemistry.

[50]  M. Pierce,et al.  Optimised chemical synthesis of 5-substituted UDP-sugars and their evaluation as glycosyltransferase inhibitors. , 2012, Carbohydrate research.

[51]  Y. Tor,et al.  Simple fluorescent pyrimidine analogues detect the presence of DNA abasic sites. , 2005, Journal of the American Chemical Society.

[52]  Hyun Seung Lee,et al.  Palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil with aryl bromides: an electrophilic metalation–deprotonation with electrophilic arylpalladium intermediate , 2011 .

[53]  E. De Clercq,et al.  Synthesis and antiviral activity of 5-thien-2-yl-2'-deoxyuridine analogues. , 1993, Journal of medicinal chemistry.

[54]  S. Pearce,et al.  Suzuki cross-coupling reactions using reverse-phase glass beads in aqueous media , 2003 .

[55]  A. Okamoto,et al.  Synthesis and ESR studies of nitronyl nitroxide-tethered oligodeoxynucleotides , 2005 .

[56]  Y. Tor,et al.  Fluorescent pyrimidine ribonucleotide: synthesis, enzymatic incorporation, and utilization. , 2007, Journal of the American Chemical Society.

[57]  C. Len,et al.  Enantiomeric d4T analogues and their structural determination , 2002 .

[58]  S. Buchwald,et al.  General catalysts for the Suzuki-Miyaura and Sonogashira coupling reactions of aryl chlorides and for the coupling of challenging substrate combinations in water. , 2005, Angewandte Chemie.

[59]  T. Fiebig,et al.  A model nucleoside for electron injection into DNA: 5-pyrenyl-2'-deoxyribose. , 2002, Angewandte Chemie.

[60]  E. Ferapontova,et al.  Synthesis and electrochemical studies of an anthraquinone-conjugated nucleoside and derived oligonucleotides. , 2009, Organic & biomolecular chemistry.

[61]  G. Wagner,et al.  A fast synthetic route to GDP-sugars modified at the nucleobase. , 2008, Chemical communications.

[62]  N. Leadbeater,et al.  Suzuki coupling of aryl chlorides with phenylboronic acid in water, using microwave heating with simultaneous cooling. , 2005, Organic letters.

[63]  L. Vrang,et al.  A new structural theme in C2-symmetric HIV-1 protease inhibitors: ortho-substituted P1/P1' side chains. , 2006, Bioorganic & medicinal chemistry.

[64]  C. Len,et al.  Diastereomeric resolution of nucleoside analogues, new potential antiviral agents, using high-performance liquid chromatography on polysaccharide-type chiral stationary phases. , 2002, Journal of chromatography. A.

[65]  C. R. Strauss,et al.  Toward rapid, "green", predictable microwave-assisted synthesis. , 2005, Accounts of chemical research.

[66]  P. Herdewijn,et al.  Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosis. , 2011, Journal of medicinal chemistry.

[67]  H. Niu,et al.  Microwave promoted palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of 6-chloropurines with sodium tetraarylborate in water , 2011 .

[68]  Akimitsu Okamoto,et al.  Synthesis and fluorescence properties of dimethylaminonaphthalene–deoxyuridine conjugates as polarity-sensitive probes , 2007 .

[69]  C. Kappe,et al.  Controlled microwave heating in modern organic synthesis. , 2004, Angewandte Chemie.

[70]  G. Wagner,et al.  Novel derivatives of UDP-glucose: concise synthesis and fluorescent properties. , 2008, Organic & biomolecular chemistry.

[71]  A. Petit,et al.  Microwave-promoted Suzuki-Miyaura cross-coupling of aryl halides with phenylboronic acid under aerobic conditions catalyzed by a new palladium complex with a thiosemicarbazone ligand , 2006 .

[72]  C. R. Strauss.  Microwave-assisted reactions in organic synthesis-are there any nonthermal microwave effects? Response to the highlight by N. Kuhnert. , 2002, Angewandte Chemie.

[73]  T. Miyasaka,et al.  Uracil and adenine nucleosides having a 2′,3′-bromovinyl structure: highly versatile synthons for the synthesis of 2′-C- and 3′-C-Branched 2′,3′-Unsaturated Derivatives , 1993 .

[74]  C. Oliver Kappe,et al.  Controlled microwave heating in modern organic synthesis: highlights from the 2004–2008 literature , 2009, Molecular Diversity.

[75]  Richard J. Fitzmaurice,et al.  Microwave enhanced synthesis , 2009 .