Synlett 2018; 29(04): 440-446
DOI: 10.1055/s-0036-1591517
letter
© Georg Thieme Verlag Stuttgart · New York

Thieme Chemistry Journals Awardees – Where Are They Now? ­Ribosylation of an Acid-Labile Glycosyl Acceptor as a Potential Key Step for the Synthesis of Nucleoside Antibiotics

Daniel Wiegmann
a   Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany   Email: christian.ducho@uni-saarland.de
,
Anatol P. Spork
b   Georg-August-University Göttingen, Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Tammannstr. 2, 37077 Göttingen, Germany
,
Giuliana Niro 
a   Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany   Email: christian.ducho@uni-saarland.de
,
Christian Ducho  *
a   Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany   Email: christian.ducho@uni-saarland.de
b   Georg-August-University Göttingen, Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Tammannstr. 2, 37077 Göttingen, Germany
› Author AffiliationsWe thank the Deutsche Forschungsgemeinschaft (DFG, SFB 803 ‘Functionality controlled by organization in and between membranes’ and grant DU 1095/5-1) and the Fonds der Chemischen Industrie (FCI, Sachkostenzuschuss) for financial support. D. W. is grateful for a doctoral fellowship of the Konrad-Adenauer-Stiftung. G. N. is grateful for a doctoral fellowship of the FCI.
Further Information

Publication History

Received: 05 October 2017

Accepted after revision: 06 October 2017

Publication Date:
12 December 2017 (online)

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Dedicated to Professor Joachim Thiem on the occasion of his birthday.

Abstract

Naturally occurring nucleoside antibiotics (e.g., muraymycins and caprazamycins) represent attractive lead structures for the development of urgently needed novel antibacterial agents. One major challenge in the total synthesis of muraymycins, caprazamycins, and their analogues is the efficient construction of the densely functionalized aminoribosylated uridine-derived core unit. In order to avoid tedious protecting-group manipulations, we have aimed to conduct the aminoribosylation step with an acid-labile glycosyl acceptor. Therefore, different glycosylation approaches have been studied, with pentenyl glycosides giving the best results.

Key words

natural products - antibiotics - nucleosides - glycosylation - ribosylation - pentenyl glycosides

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591517.
  • Supporting Information
 

  • References and Notes

  • 2 Walsh C. Nat. Rev. Microbiol. 2003; 1: 65
    CrossrefPubMedSearch in Google Scholar
  • 6 McDonald LA. Barbieri LR. Carter GT. Lenoy E. Lotvin J. Petersen PJ. Siegel MM. Singh G. Williamson RT. J. Am. Chem. Soc. 2002; 124: 10260
    CrossrefPubMedSearch in Google Scholar
  • 7 Igarashi M. Nakagawa N. Doi S. Hattori N. Naganawa H. Hamada M. J. Antibiot. 2003; 56: 580
    CrossrefPubMedSearch in Google Scholar
  • 14 Spork AP. Ducho C. Synlett 2013; 24: 343
    Thieme ConnectSearch in Google Scholar
  • 15 Brechbühler H. Büchi H. Hatz E. Schreiber J. Eschenmoser A. Helv. Chim. Acta 1965; 48: 1746
    CrossrefSearch in Google Scholar
  • 16 Naresh K. Bharati BK. Avaji PG. Chatterji D. Jayaraman N. Glycobiology 2011; 21: 1237
    CrossrefPubMedSearch in Google Scholar
  • 18 Gravier-Pelletier C. Ginisty M. Le Merrer Y. Tetrahedron: Asymmetry 2004; 15: 189
    CrossrefSearch in Google Scholar
  • 20 Gelin M. Ferrieres V. Plusquellec D. Eur. J. Org. Chem. 2000; 1423
  • 22 Ludewig M. Thiem J. Synthesis 1998; 56
    Thieme Connect
  • 23 Zhang Y. Knapp S. J. Org. Chem. 2016; 81: 2228
    CrossrefPubMedSearch in Google Scholar
    • 24a Fraser-Reid B. Udodong UE. Wu Z. Ottosson H. Merritt JR. Rao CS. Roberts C. Madsen R. Synlett 1992; 927
      Thieme Connect
    • 24b Fraser-Reid B. Merritt JR. Handlon AL. Andrews CW. Pure Appl. Chem. 1993; 65: 779
      CrossrefSearch in Google Scholar
  • 25 Synthesis of Protected Ribosylated (5′S,6′S)-GlyU 4To a solution of the glycosyl donor β-18 (20.1 mg, 64.5 μmol) and the (5′S,6′S)-GlyU-derived acceptor 2 (35.6 mg, 48.4 μmol) in CH2Cl2 (3 mL) with freshly activated molecular sieves (4 Å), NIS (18.9 mg, 83.9 μmol) was added at r.t. under exclusion of light. Over 10 min, TESOTf (5.8 μL, 26 μmol, 1% solution in CH2Cl2) was added dropwise. The reaction mixture was stirred at r.t. for 15 min before ice (5 g) was added and the mixture was allowed to warm to r.t. again. It was then diluted with CH2Cl2 (70 mL) and the organic layer was washed with 10% Na2S2O3 solution (1 × 70 mL), sat. NaHCO3 solution (1 × 70 mL), and brine (1 × 70 mL). The organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure. The resultant crude product was purified by column chromatography (PE–EtOAc, 75:25 → 70:30) to give 4 (16.6 mg, 36%, 58% brsm) as a colorless solid; mp 72 °C. TLC: Rf = 0.28 (i-hexane–EtOAc, 7:3). [α]D 20 –7.0 (c 0.7, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 0.07 (s, 3 H, SiCH3), 0.08 (s, 3 H, SiCH3), 0.09 (s, 3 H, SiCH3), 0.13 (s, 3 H, SiCH3), 0.83 (t, J = 7.5 Hz, 3 H, 1iv-H), 0.88 (t, J = 7.5 Hz, 3 H, 5iv-H), 0.90 (s, 9 H, SiC(CH3)3), 0.90 (s, 9 H, SiC(CH3)3), 1.45 (s, 9 H, OC(CH3)3), 1.53 (q, J = 7.4 Hz, 2 H, 2iv-H), 1.66 (dq, J = 7.4, 1.8 Hz, 2 H, 4iv-H), 3.55 (dd, J = 13.0, 4.0 Hz, 1 H, 5′′′-Ha), 3.72 (dd, J = 13.0, 3.9 Hz, 1 H, 5′′′-Hb), 3.94 (dd, J = 5.7, 4.1 Hz, 1 H, 3′-H), 4.13 (dd, J = 5.7, 2.3 Hz, 1 H, 4′-H), 4.16 (dd, J = 4.1, 3.6 Hz, 1 H, 2′-H), 4.31–4.34 (m, 1 H, 4′′′-H), 4.39 (dd, J = 2.3, 1.9 Hz, 1 H, 5′-H), 4.48 (d, J = 6.3 Hz, 1 H, 2′′′-H), 4.51 (dd, J = 9.2, 1.9 Hz, 1 H, 6′-H), 4.64 (dd, J = 6.3, 1.4 Hz, 1 H, 3′′′-H), 4.97 (d, J = 12.1 Hz, 1 H, 1′′-Ha), 5.14 (s, 1 H, 1′′′-H), 5.24 (d, J = 12.1 Hz, 1 H, 1′′-Hb), 5.44 (d, J = 3.6 Hz, 1 H, 1′-H), 5.60 (dd, J = 8.2, 2.1 Hz, 1 H, 5-H), 6.15 (d, J = 9.2 Hz, 1 H, 6′-NH), 7.24–7.36 (m, 5 H, aryl-H), 7.82 (d, J = 8.2 Hz, 1 H, 6-H), 8.02 (d, J = 2.1 Hz, 1 H, 3-NH). 13C NMR (126 MHz, CDCl3): δ = –4.9, –4.8, –4.2, –3.9, 7.6, 8.5, 18.1, 18.2, 26.0, 26.0, 28.1, 28.9, 29.4, 53.5, 56.5, 67.0, 71.5, 74.8, 77.8, 81.8, 82.7, 85.3, 86.0, 86.4, 90.6, 101.1, 112.3, 117.9, 128.3, 128.4, 127.7, 136.8, 140.8, 149.9, 156.4, 162.9, 168.8. HRMS (ESI+): m/z calcd for C45H73N6O13Si2: 961.4769 [M + H]+; found: 961.4778. IR (ATR): ν = 2930, 2857, 2104, 1685, 1457, 1253, 1160, 1059, 835, 775 cm–1. UV (MeCN): λmax = 261 nm.