Elsevier

Tetrahedron

Volume 64, Issue 32, 4 August 2008, Pages 7453-7475
Tetrahedron

Tetrahedron report number 841
Synthesis of cyclonucleosides having a C–C bridge

https://doi.org/10.1016/j.tet.2008.04.095Get rights and content

Graphical abstract

The synthesis of cyclonucleosides having a C–C bridge is reviewed. The report contains 54 references

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Introduction

Natural nucleosides are of great biological importance in metabolic pathways.1, 2 The typical structure of nucleosides has two molecular fragments: d-ribo- or d-2′-deoxyribopentofuranose as the sugar moiety and a purine or pyrimidine aglycone. These two moieties are covalently bonded from N1 of pyrimidine (uracil, thymine and cytosine) or N9 of purine (adenine and guanine) to C1′ of the glycone in a β-configuration (Fig. 1).

The molecular geometry of nucleosides induces different conformations, which usually involve the determination of three principal structural parameters:3 (i) the glycosyl torsion angle χ (O4′-C1′-N9-C4 for a purine nucleoside and O4′-C1′-N1-C2 for a pyrimidine nucleoside), which determines the syn or anti disposition of the nucleobase relative to the sugar moiety (syn when the C2 carbonyl of pyrimidines or N3 of purines lies over the sugar ring and anti for the opposite direction); (ii) the torsion angle γ (O5′C5′C4′C3′), which determines the position of the 5′-OH relative to the C3′ carbon atom (+sc, ap, −sc rotamers); and (iii) the phase angle of pseudorotation P (0–360°) and the maximum out-of-plane pucker υmax (0–50°), which determine the puckering of the furanose ring and its deviation from planarity, respectively.4, 5 The value of P depends up on the five endocyclic sugar torsion angles (υ0υ4) and on the puckering of the furanose ring. The conformation of the furanose ring around the pseudorotational cycle alternates every 18° between the envelope (E) and twist (T) form. The conformations of the nucleoside described by these three-state models (χ, γ, P) are in interdependent equilibria determined by steric and stereoelectronic effects (e.g., anomeric and gauche effects)6 and the energy barriers between the preferred conformational states are usually low (Fig. 2).

In an enzymatic reaction, the problem is to correlate the conformational preference demanded by the specific enzyme in the activation pathway with a particular nucleoside conformation because the nucleoside conformation in solution can differ sharply from that determined in the solid state. Consequently, any conformation–activity study based exclusively on solid-state conformational parameters would be flawed, unless both solution and solid-state conformations are known to be equivalent. One strategy for pre-organising the nucleoside conformation might be to rigidify the normally flexible nucleoside by chemical modification. To overcome this problem, the limitation of conformation of a nucleoside or nucleotide is widely used to reach a particular conformation of a rotamer to study: (i) the affinity of a biomacromolecule for its natural ligand;7, 7(a), 7(b), 7(c), 7(d), 7(e), 7(f), 7(g), 7(h), 7(i), 7(j), 7(k), 7(l) and (ii) the molecular recognition in an oligonucleotide chain (RNA/DNA).8, 8(a), 8(b), 8(c), 8(d), 8(e), 8(f), 8(g) This particular conformation can be predetermined by limiting the conformational equilibrium (syn or anti, North or South, +sc, ap or −sc) by the elaboration of restricted polycyclic structures. Nucleosides with a restricted conformation can be classified into three families: (i) bicyclonucleosides obtained by bonding two atoms of the furanose moiety via an alkylene unit or analogue; (ii) cyclic phosphoesters obtained by forming an alkylene bridge or analogue between the phosphorus atom and the nucleobase or the furanose moiety; and (iii) cyclonucleosides obtained by bonding one atom of the furanose moiety and one atom of the nucleobase via an alkylene unit or analogue (Fig. 3).

For the sake of clarity, this review has been arranged to describe the synthesis of cyclonucleosides having an alkylene group between the glycone moiety and the nucleobase.

Section snippets

Radical reactions

The synthesis of cyclonucleosides has been reported by the generation of a radical using chemical and photochemical initiation. In the first case, the formation of a radical at a position of the glycone moiety and intramolecular radical addition at a carbon atom of the nucleobase were described. In the second case, the formation of a radical at either a position of the glycone moiety or the nucleobase followed by intramolecular radical addition was developed.

Ueda et al.9 reported the synthesis

Conclusions

A major initiative to synthesise cyclonucleosides has been led by attempts to discover compounds with increased activity over natural nucleos(t)ides or nucleos(t)ide analogues to provide structure–activity data. To date, the majority of work has been directed towards cyclonucleosides having a linker: (i) at either the 6,5′-, 6,3′-, 6,2′-, or 6,1′-position in the field of pyrimidine nucleosides; and (ii) at either the 8,5′-, 8,3′-, 8,2′-, or 8,1′-position in the field of purine nucleosides. Most

Christophe Len was born in L'Isle Adam (France) in 1966. He received his Ph.D. from the University of Picardie-Jules Verne (UPJV) in Amiens (France) under the supervision of Professor P. Villa in the field of carbohydrate chemistry. In 1996, he joined Doctor G. Mackenzie's group at the University of Hull (UK) as a post-doctoral fellow to work on the synthesis of nucleoside analogues. In 1997, he became Maître de Conférences at UPJV and worked on the chemistry of antiviral nucleoside analogues

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References and notes (54)

  • E. De Clercq

    J. Clin. Virol.

    (2004)
  • T. Sano et al.

    Chem. Pharm. Bull.

    (1985)
  • M.L. Navacchia et al.

    Eur. J. Org. Chem.

    (2005)
  • Y. Yoshimura et al.

    Synlett

    (2007)
  • D.H.R. Barton et al.

    Tetrahedron

    (1991)
  • M.O. Bevierre et al.

    Bioorg. Med. Chem. Lett.

    (1994)
  • A. Matsuda et al.

    Nucleic Acids Res.

    (1984)
  • A. Matsuda et al.

    Cancer Sci.

    (2004)
  • W. Saenger

    Principles of Nucleic Acid Structure

    (1984)
  • C. Altona et al.

    J. Am. Chem. Soc.

    (1973)
  • C. Altona et al.

    J. Am. Chem. Soc.

    (1972)
  • J. Plavec et al.

    J. Am. Chem. Soc.

    (1993)
  • Recent...M.H. Sorensen et al.

    J. Org. Chem.

    (2001)
    Y. Choi et al.

    J. Med. Chem.

    (2003)
    Y. Choi et al.

    Nucleosides, Nucleotides Nucleic Acids

    (2003)
    V.E. Marquez et al.

    J. Am. Chem. Soc.

    (2004)
    P. Russ et al.

    J. Med. Chem.

    (2003)
    V.E. Marquez et al.

    J. Am. Chem. Soc.

    (2005)
    L. Zalah et al.

    Antiviral Res.

    (2002)
    R.G. Ravi et al.

    Bioorg. Med. Chem. Lett.

    (2001)
    H.S. Kim et al.

    J. Med. Chem.

    (2002)
    S. Costanzi et al.

    J. Med. Chem.

    (2005)
    K.A. Jacobson et al.

    J. Med. Chem.

    (2005)
    J.A. Lee et al.

    J. Org. Chem.

    (2005)
  • Recent...R. Steffens et al.

    J. Am. Chem. Soc.

    (1997)
    E.T. Kool

    Chem. Rev.

    (1997)
    P. Herdewijn

    Biochim. Biophys. Acta

    (1999)
    M. Meldgaard et al.

    J. Chem. Soc., Perkin Trans. 1

    (2000)
    C. Leumann

    Bioorg. Med. Chem.

    (2002)
    L. Kvaerno et al.

    Chem. Commun.

    (2001)
    J. Wengel

    Acc. Chem. Res.

    (1999)
  • T. Ueda et al.

    Chem. Pharm. Bull.

    (1984)
  • T. Ueda et al.

    Nucleic Acids Res.

    (1981)
  • T.H. Ueda et al.

    Heterocycles

    (1982)
  • Y. Suzuki et al.

    Chem. Pharm. Bull.

    (1987)
  • T.H. Ueda et al.

    Nucleosides Nucleotides

    (1984)
  • T. Ueda et al.

    Nucleosides Nucleotides

    (1985)
  • T. Ueda et al.

    Nucleic Acids Res.

    (1982)
  • H. Usui et al.

    Chem. Pharm. Bull.

    (1986)
  • Y. Yoshimura et al.

    Chem. Pharm. Bull.

    (1992)
  • Y. Yoshimura et al.

    Tetrahedron Lett.

    (1991)
  • L.Y. Hsu et al.

    Chin. Pharm. J.

    (1991)
  • T. Sano et al.

    Chem. Pharm. Bull.

    (1985)
  • G.C. Magnin et al.

    Nucleosides Nucleotides

    (1999)
  • Cited by (0)

    Christophe Len was born in L'Isle Adam (France) in 1966. He received his Ph.D. from the University of Picardie-Jules Verne (UPJV) in Amiens (France) under the supervision of Professor P. Villa in the field of carbohydrate chemistry. In 1996, he joined Doctor G. Mackenzie's group at the University of Hull (UK) as a post-doctoral fellow to work on the synthesis of nucleoside analogues. In 1997, he became Maître de Conférences at UPJV and worked on the chemistry of antiviral nucleoside analogues specialising on those with novel glycone systems. In 2003, he received his habilitation and was promoted to full Professor in 2004 at the University of Poitiers (France). His current main research interests are in the total synthesis of natural products and bioactive molecules, which include carbohydrates and nucleoside analogues having restricted conformations.

    Martine Mondon was born in 1949 in Talence (France). She received her ‘doctorat de 3ème cycle’ from the University of Paris VI under the direction of Dr Claude Wakselman (1973) for her work on the chemistry of lithium dialkylcuprates, and her Ph.D. from the University of Sherbrooke (Canada) under the direction of Professor Jean Lessard (1977) for her work on radical and photochemical addition of N-haloamides to olefins. She entered the Centre National de la Recherche Scientifique (CNRS) in 1978 and joined the group of Professor Jean-Pierre Gesson in Poitiers (France) to develop the synthesis, transformation and reactivity of natural products. In 2004, she worked in Professor Christophe Len's group in the field of nucleoside analogues having restricted conformations.

    Jacques Lebreton was born in Guérande (France) in 1960. He received his Ph.D. degree (1986) from the University of Paris XI-Orsay under the supervision of Professor Eric Brown (Le Mans). His thesis work included the total synthesis of C-nor d-homosteroids. In 1986, he started his first post-doctoral fellowship with Professor James A. Marshall at the University of South Carolina working on the [2,3]-Wittig rearrangement and its application in total synthesis. Following a second post-doctoral fellowship with Professor Robert E. Ireland at the University of Virginia working on the total synthesis of monensine, he joined in 1990 the laboratories of CIBA-GEIGY (Novartis) in Basle, where he worked in Dr. Alain De Mesmaeker's group in the field of antisens. In 1994, he joined the CNRS and spent a few years in the group of Dr. Jean Villiéras (UMR CNRS 6513, Nantes) concerned with organometallic chemistry. In 1998, he was promoted to Professor at the University of Nantes. His major research interests are organometallic chemistry and medicinal chemistry. In 2000 with his friend and colleague A. Guingant, he set up a research group, named Symbiose, devoted to developing research at the interface between chemistry and biology. Most of his recent work has focussed on the synthesis of bioactive molecules, such as steroids, nucleosides, alkaloids, macrolides and azasugars, for biological evaluation purposes in the fields of HIV, central nervous system diseases and cancer through academic and industrial collaborations. His research efforts also include the synthesis of labelled molecules to study biological processes.

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