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Synlett 2017; 28(07): 831-834
DOI: 10.1055/s-0036-1588937
letter
© Georg Thieme Verlag Stuttgart · New York

Preparation of 2′-Alkylselenouridine Derivatives via a 2-(Trimethyl­silyl)ethylselenation Approach

Shota Fukuno
a   Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan   eMail: koketsu@gifu-u.ac.jp
,
Masayuki Ninomiya
a   Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan   eMail: koketsu@gifu-u.ac.jp
b   Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
,
Mamoru Koketsu*
a   Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan   eMail: koketsu@gifu-u.ac.jp
b   Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
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Publikationsverlauf

Received: 22. November 2016

Accepted after revision: 22. Dezember 2016

Publikationsdatum:
17. Januar 2017 (online)

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Abstract

2′-O-Methylation of nucleotides is well-known to increase siRNA stability against nuclease activities. Recently, selenium-containing biomolecules have been recognized as unique biological and medicinal agents for humans. In this study, 2′-alkylselenouridine derivatives were prepared through 2-(trimethylsilyl)ethylselenation at the C2′ position of 5′-DMT-2,2′-O-cyclouridine, followed by alkylation with various haloalkanes utilizing the characteristics of a Si atom. Overall, we demonstrated the versatility of a 2-(trimethylsilyl)ethylselenyl group for the synthesis of 2′-alkylselenouridines.

Key words

selenium-containing biomolecule - 2-(trimethylsilyl)ethyl­selenyl group - selenation - 2′-alkylselenouridine derivative - phosphoramidite monomer

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588937.
  • Supporting Information
 

  • References and Notes

  • 1 Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Nature (London, UK) 1998; 391: 806
    Crossref
  • 2 Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Nature (London, UK) 2001; 411: 494
    Crossref
  • 3 Rana TM. Nat. Rev. Mol. Cell. Biol. 2007; 8: 23
    Crossref
  • 4 Chiu Y.-L, Rana TM. RNA 2003; 9: 1034
    CrossrefPubMed
  • 5 Castanotto D, Rossi JJ. Nature (London, UK) 2009; 457: 426
    Crossref
  • 6 Lesnik EA, Guinosso CJ, Kawasaki AM, Sasmor H, Zounes M, Cummins LL, Ecker DJ, Cook PD, Freier SM. Biochemistry 1993; 32: 7832
    CrossrefPubMed
  • 7 Cummins LL, Owens SR, Risen LM, Lesnik EA, Freier SM, McGee D, Guinosso CJ, Cook PD. Nucleic Acids Res. 1995; 23: 2019
    CrossrefPubMed
  • 8 Freier SM, Altmann KH. Nucleic Acids Res. 1997; 25: 4429
    CrossrefPubMed
  • 9 Morita K, Takagi M, Hasegawa C, Kaneko M, Tsutsumi S, Sone J, Ishikawa T, Imanishi T, Koizumi M. Bioorg. Med. Chem. 2003; 11: 2211
    CrossrefPubMed
  • 10 Watts JK, Deleavey GF, Damha MJ. Drug Discov. Today 2008; 13: 842
    CrossrefPubMed
  • 11 Czauderna F, Fechtner M, Dames S, Aygün H, Klippel A, Pronk GJ, Giese K, Kaufmann J. Nucleic Acids Res. 2003; 31: 2705
    CrossrefPubMed
  • 12 Rayman MP. Lancet 2000; 356: 233
    CrossrefPubMed
  • 13 Rayman MP. Lancet 2012; 376: 1256
  • 14 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Science 1973; 179: 588
    CrossrefPubMed
  • 15 Brigelius-Flohé R, Maiorino M. Biochim. Biophys. Acta 2013; 1830: 3289
    CrossrefPubMed
  • 16 Ninomiya M, Garud DR, Koketsu M. Coord. Chem. Rev. 2011; 255: 2968
    Crossref
  • 17 Kogami M, Koketsu M. Org. Biomol. Chem. 2015; 13: 9405
    CrossrefPubMed
  • 18 Kogami M, Davis DR, Koketsu M. Heterocycles 2016; 92: 64
    Crossref
  • 19 Du Q, Carrasco N, Teplova M, Wilds CJ, Egli M, Huang Z. J. Am. Chem. Soc. 2002; 124: 24
    CrossrefPubMed
  • 20 Höbartner C, Micura R. J. Am. Chem. Soc. 2004; 126: 1141
    CrossrefPubMed
  • 21 Moroder H, Kreutz C, Lang K, Serganov A, Micura R. J. Am. Chem. Soc. 2006; 128: 9909
    CrossrefPubMed
  • 22 Synthesis of 5′-(4,4′-Dimethoxytrityl)-2′-trimethylsilylethyl­uridine (4) After stirring of 2-(trimethylsilyl)ethyl diselenide (1, 1.14 mmol), NaBH4 (1.14 mmol), and EtOH (2.85 mmol) in DMF (5 mL) at 0 °C for 30 min, 3 (0.95 mmol) was added to the solution, and the reaction was continued at 60 °C for an additional 1 h. The resultant solution was quenched by 5% NH3Cl aq, and then was poured into distilled water, partitioned with EtOAc, and washed with brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluted with n-hexane–EtOAc (3:1 to 1:1) to afford 4 (98% yield) as a white amorphous powder. [α]D +79.39 (c 0.64, CHCl3). IR (film): νmax = 3407, 2924, 1685 cm–1. 1H NMR (600 MHz, CDCl3): δ = 8.79 (br s, 1 H, NH), 7.89 (d, 1 H, J = 7.6 Hz, H5), 7.36 (d, 2 H, J = 6.8 Hz, Ph), 7.30 (t, 2 H, J = 7.6 Hz, Ph), 7.26–7.23 (m, 5 H, Ph), 6.84 (d, 4 H, J = 8.9 Hz, Ph), 6.19 (d, 1 H, J = 8.3 Hz, H1′), 5.36 (d, 1 H, J = 8.2 Hz, H6), 4.37 (dd, 1 H, J = 2.8, 4.8 Hz, H3′), 4.18 (d, 1 H, J = 2.7 Hz, H4′), 3.79 (s, 6 H, 2 OMe), 3.66 (dd, 2 H, J = 4.8, 7.6 Hz, H2′), 3.51 (dd, 1 H, J = 2.7, 11.0 Hz, H5′a), 3.47 (dd, 2 H, J = 2.7, 11.0 Hz, H5′b), 2.85 (d, 1 H, J = 3.5 Hz, OH), 2.78–2.71 (m, 2 H, SeCH2 CH2TMS), 1.03–0.95 (m, 2 H, SeCH2CH2 TMS), 0.008 (s, 9 H, SiMe3). 13C NMR (150 MHz, CDCl3): δ = 163.1, 158.9, 150.4, 144.4, 140.0, 135.2, 135.0, 130.21, 130.16, 128.2, 127.4, 113.5, 102.7, 88.1, 87.4, 84.7, 71.6, 63.5, 55.4, 50.4, 20.8, 19.2, –1.8. 77Se NMR (115 MHz, CDCl3): δ = 150.3. HRMS (ESI, TOF): m/z calcd for C35H42N2O7SeNa, 733.1824; found: 733.1816 [M + Na]+.
  • 23 Alkylation of 6 TBAF (1.0 M in THF, 0.15 mmol) was added to a solution of 6 (0.05 mmol) and MeI (0.25 mmol) in DMF (0.5 ml). After stirring at 40 °C for 5 h, the resultant solution was poured into distilled water, partitioned with EtOAc twice, and washed with brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluted with n-hexane–EtOAc (3:1 to 2:1) to afford 7a (92% yield) as a white amorphous powder. Reaction parameters are given in Tables 1 and 2. The operation procedures for 7b–s are exactly the same with 7a. [α]D +52.18 (c 0.62, CHCl3). IR (film): νmax = 3398, 2925, 1713, 1661 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.78 (d, 1 H, J = 8.0 Hz, H5), 7.38–7.25 (m, 14 H, Ph), 6.84 (d, 4 H, J = 8.9 Hz, Ph), 6.21 (d, 1 H, J = 6.7 Hz, H1′), 5.47 (s, 2 H, CH2OCH2 Ph), 5.40 (d, 1 H, J = 8.1 Hz, H6), 4.69 (s, 2 H, CH2 OCH2Ph), 4.38 (d, 1 H, J = 5.4 Hz, H3′), 4.15 (d, 1 H, J = 3.5 Hz, H4′), 3.79 (s, 6 H, 2 OMe), 3.55–3.46 (m, 3 H, H2′ and H5′), 2.75 (d, 1 H, J = 4.0 Hz, OH), 2.14 (s, 3 H, SeMe). 13C NMR (100 MHz, CDCl3): δ = 162.7, 158.9, 151.3, 144.3, 138.5, 138.0, 135.3, 135.1, 130.2, 128.4, 128.2, 127.8, 127.4, 113.4, 102.4, 102.3, 88.8, 87.4, 84.5, 72.3, 71.3, 70.5, 63.0, 55.4, 51.0, 4.9. 77Se NMR (75 MHz, CDCl3): δ = 27.9. HRMS (ESI, TOF): m/z calcd for C39H40N8O7SeNa: 767.1848; found: 767.1860 [M + Na]+.
  • 24 Grundberg H, Andergran M, Nilsson UJ. Tetrahedron Lett. 1999; 40: 1811
    Crossref
  • 25 Beaucage SL, Iyer RP. Tetrahedron 1993; 49: 6123
    Crossref
  • 26 Venkatesan N, Kim SJ, Kim BH. Curr. Med. Chem. 2003; 10: 1973
    CrossrefPubMed
  • 27 Cobb AJ. Org. Biomol. Chem. 2007; 5: 3260
    Crossref
  • 28 Kachalova A, Zubin E, Stetsenko D, Gait M, Oretskaya T. Org. Biomol. Chem. 2004; 2: 2793
    CrossrefPubMed
  • 29 Sinha ND, Biernat J, Köester H. Tetrahedron Lett. 1983; 24: 5843
    Crossref
  • 30 Nicolas C, Yuri B, Elizabeth T, Elizer H, Zhen H. Nucleic Acids Res. 2004; 32: 1638
    CrossrefPubMed