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Synlett 2023; 34(19): 2315-2318
DOI: 10.1055/a-2132-1938
letter

Synthesis of Superarmed Thioglycosides via the Ring Opening of 1,2-Orthoesters

Zoe Beato
a   Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
b   BiOrbic, Bioeconomy SFI research centre, University College Dublin, Belfield, Dublin 4, Ireland
,
Xiangming Zhu∗
a   Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
b   BiOrbic, Bioeconomy SFI research centre, University College Dublin, Belfield, Dublin 4, Ireland
› Author AffiliationsThis research was supported by BiOrbic, Bioeconomy SFI Research Centre, which is funded by Ireland's European Structural and Investment Programmes, Science Foundation Ireland (16/RC/ 3889, 18/EPSRC-CDT/3582) and the European Regional Development Fund.
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Abstract

Since the advent of the armed–disarmed strategy, thioglycosides have become essential tools in one-pot oligosaccharide synthesis. The continuum of glycosyl donor reactivity has since been expanded to include so-called ‘superarmed’ thioglycoside donors whose reactivity relies on more than just the inductive effects of protecting groups. Here we report a new method for the synthesis of superarmed thioglycosides via the ring opening of 1,2-orthoesters. This method ensures the necessary 1,2-trans stereochemistry, and importantly, makes use of trimethylsilyl thioethers as sulfur nucleophiles to avoid the use of unpleasant free thiols. Ten examples of ethyl and phenyl thioglycosides of mono- and disaccharides were synthesised from their orthoesters using tris(pentafluorophenyl)borane (BCF) as the Lewis acid promoter and were obtained in good yield and purity.

Key words

thioglycoside - superarmed - BCF - orthoester - stereoselective

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2132-1938.
  • Supporting Information


Publication History

Received: 21 June 2023

Accepted after revision: 18 July 2023

Accepted Manuscript online:
18 July 2023

Article published online:
20 September 2023

© 2023. Thieme. All rights reserved

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  • References and Notes

  • 1 Lian G, Zhang X, Biao Y. Carbohydr. Res. 2015; 403: 13
    CrossrefPubMed
  • 2 Zhu XM, Schmidt RR. Angew. Chem. Int. Ed. 2009; 48: 1900
    CrossrefPubMed
  • 3 Mootoo DR, Konradsson P, Udodong U, Fraser-Reid B. J. Am. Chem. Soc. 1988; 110: 5583
    Crossref
    • 4a Codée JD. C, Litjens RE. J. N, van den Bos LJ, Overkleeft HS, van der Marel GA. Chem. Soc. Rev. 2005; 34: 769
      CrossrefPubMed
    • 4b Cao S, Gan Z, Roy R. Carbohydr. Res. 1999; 318: 75
      CrossrefPubMed
    • 4c Jensen HH, Pedersen CM, Bols M. Chem. Eur. J. 2007; 13: 7576
      CrossrefPubMed
    • 4d Kamat MN, Demchenko AV. Org. Lett. 2007; 7: 3215
      CrossrefPubMed
    • 6a Mydock LK, Demchenko AV. Org. Lett. 2008; 10: 2107
      CrossrefPubMed
    • 6b Premathilake HD, Mydock LK, Demchenko AV. J. Org. Chem. 2010; 75: 1095
      CrossrefPubMed
    • 7a Li J, Wang M, Zhang X. Org. Lett. 2021; 23: 9053
      CrossrefPubMed
    • 7b Wang LX, Sakairi N, Kuzuhara H. J. Chem. Soc., Perkin Trans. 1 1990; 1677
      Crossref
    • 8a Tiwari VK, Kumar A, Schmidt RR. Eur. J. Org. Chem. 2012; 2945
      Crossref
    • 8b Uriel C, Ventura J, Gómez AM, López C, Frasier-Reid B. Eur. J. Org. Chem. 2012; 3122
      Crossref
    • 8c Pozsgay V, Kubler-Kielb J, Coxon B, Santacroce P, Robbins JB, Schneerson R. J. Org. Chem. 2012; 77: 5922
      CrossrefPubMed
    • 8d Kaeothip S, Demchenko AV. Carbohydr. Res. 2011; 346: 1371
      CrossrefPubMed
  • 9 Kong F. Carbohydr. Res. 2007; 342: 345
    CrossrefPubMed
    • 10a Garegg PJ, Konradsson P, Kvarnstrom I, Norberg T, Svensson SC. T, Wigilius B. Acta Chem. Scand. B 1985; 39: 569
      Crossref
    • 10b Uriel C, Ventura J, Gómez AM, López C, Frasier-Reid B. J. Org. Chem. 2012; 77: 795
      CrossrefPubMed
  • 11 Kafle A, Liu J, Ciu L. Can. J. Chem. 2016; 94: 894
    CrossrefPubMed
  • 12 Kong F. Curr. Org. Chem. 2003; 7: 841
    CrossrefPubMed
    • 13a General Procedure for the Formation of Ethyl 2-O-Acetyl Thioglycosides A sugar orthoester (0.20 mmol) was dried under high vacuum for 1 h. The flask was flushed with N2, and dry CH2Cl2 (5 mL) was added. The flask was cooled to 0 °C and (ethylthio)trimethylsilane (72 μL, 0.44 mmol, 2.2 equiv) was added followed by tris(pentafluorophenyl)borane (0.150 g, 0.30 mmol, 1.5 equiv). The mixture was stirred at 0 °C for 5 min. The reaction was neutralised with triethylamine (0.1 mL) and then concentrated in vacuo. The crude mixture was purified by flash chromatography (cHex/EtOAc, 8:1) to give the product as a colorless solid. Compound 6a was obtained as a colorless solid (0.074 g, 0.139 mmol, 70%). 1H NMR (500 MHz, CDCl3): δ = 7.38–7.27 (m, 13 H, ArCH), 7.20 (dd, J = 7.3, 2.1 Hz, 2 H, ArCH), 5.06 (dd, J = 10.1, 9.0 Hz, 1 H, H-2), 4.82 (dd, J = 11.1, 7.5 Hz, 2 H, benzyl CH2), 4.71 (d, J = 11.4 Hz, 1 H, benzyl CH2), 4.65–4.55 (m, 3 H, benzyl CH2), 4.38 (d, J = 10.0 Hz, 1 H, H-1), 3.78 (dd, J = 11.1, 2.0 Hz, 1 H, H-6a), 3.75–3.67 (m, 3 H, H-3, H-4, H-6b), 3.52 (ddt, J = 6.7, 4.5, 2.1 Hz, 1 H, H-5), 2.80–2.65 (m, 2 H, SCH2), 2.00 (s, 3 H,C(O)CH3), 1.28 (t, J = 7.5 Hz, 3 H, S(CH2)CH3) ppm. 13C NMR (126 MHz, CDCl3): δ = 169.8 (C=O), 138.3, 138.3, 138.0 (ArC), 128.6, 128.5, 128.2, 128.0, 127.9, 127.9, 127.8, 127.7 (ArCH), 84.5 (C-3), 83.5 (C-1), 79.6 (C-5), 78.0 (C-4), 75.4 (benzyl CH2), 75.2 (benzyl CH2), 73.6 (benzyl CH2), 71.9 (C-2), 69.0 (C-6), 23.9 (SCH2), 21.1 (acetyl CH3), 15.0 (SCH2 CH3) ppm.

      • Spectra matched literature reports:
    • 13b Ple K, Chwalek M, Voutquenne-Nazabadioko L. Tetrahedron 2005; 61: 4347
      Crossref
    • 14a Ethyl-2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-β-d-glucopyranoside (9a) Orthoester 4 (0.20 mmol) was dried under high vacuum for 1 h. The flask was flushed with N2, and dry CH2Cl2 (5 mL) was added. The flask was cooled to 0 °C and (ethylthio)trimethylsilane (72 μL, 0.44 mmol, 2.2 equiv) was added followed by tris(pentafluorophenyl)borane (0.150 g, 0.30 mmol, 1.5 equiv). The mixture was brought to rt and stirred for 4 h. The reaction was neutralised with triethylamine (0.1 mL) then concentrated in vacuo. The crude mixture was purified by flash chromatography (cHex/EtOAc, 8:1) to give the product as a colourless solid (0.11 g, 0.18 mmol, 61%). 1H NMR (400 MHz, CDCl3): δ = 8.05–8.00 (m, 2 H, ArH), 7.57 (t, J = 7.4 Hz, 1 H, ArH), 7.47–7.41 (m, 2 H, ArH), 7.37–7.26 (m, 8 H, ArH), 7.21–7.17 (m, 2 H, ArH), 7.16–7.08 (m, 5 H, ArH), 5.31 (dd, J = 10.0, 8.9 Hz, 1 H, H-2), 4.82 (d, J = 10.9 Hz, 1 H, benzyl CH2), 4.74 (d, J = 11.1 Hz, 1 H, benzyl CH2), 4.66 (d, J = 11.1 Hz, 1 H, benzyl CH2), 4.63 (d, J = 12.0 Hz, 1 H, benzyl CH2), 4.61–4.55 (m, 2 H, benzyl CH2), 4.53 (d, J = 10.1 Hz, 1 H, H-1), 3.84 (t, J = 8.9 Hz, 1 H, H-3), 3.81–3.71 (m, 3 H, H-4, H6a+b), 3.60–3.55 (m, 1 H, H-5), 2.73 (qd, J = 12.3, 7.4 Hz, 2 H, SCH2), 1.24 (t, J = 7.5 Hz, 3 H, SCH2CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 165.4 (C=O), 138.3, 138.1, 137.9 (ArC), 133.3 (ArCH), 130.1 (ArC), 130.0, 128.6, 128.5, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.8 (ArCH, 84.5 (C-3), 83.6 (C-1), 79.7 (C-5), 78.1 (C-4), 75.4 (benzyl CH2), 75.3 (benzyl CH2), 73.6 (benzyl CH2), 72.6 (C-2), 69.1 (C-6), 24.0 (SCH2), 15.1 (SCH2 CH3) ppm.

      • Spectra match literature reports:
    • 14b Poulsen LT, Heuckendorff M, Jensen HH. Org. Biomol. Chem. 2018; 16: 2269
      CrossrefPubMed