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Synlett 2023; 34(03): 288-292
DOI: 10.1055/a-1969-3992
letter

Total Synthesis of Phellinus ribis Glycans with Immunostimulating Activities by an Orthogonal One-Pot Glycosylation Strategy

Jie Wan‡
,
Leilei Wang‡
,
Guozhi Xiao  ∗
The research was supported by National Natural Science Foundation of China (22271294), the Key Project of the Natural Science Foundation of Yunnan Province (No. 202101AS070030), the CAS Pioneer Hundred Talents Program (No. 2017-128), the Young Talents Project of High-level Talent Introduction Program of Yunnan Province.
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Abstract

A total synthesis of nonasaccharide repeating units and shorter sequences from Phellinus ribis glycans with strong immunostimulating activities was achieved by an orthogonal one-pot glycosylation strategy based on an N-phenyltrifluoroacetimidate glycosylation, a Yu glycosylation, and an ortho-(1-phenylvinyl)benzoate glycosylation. The issues inherent to thioglycosides-based orthogonal one-pot glycosylations, such as aglycone transfer, are eliminated by this one-pot glycosylation strategy, which streamlines the chemical synthesis of glycans.

Key words

Phellinus ribis - glycans - one-pot reaction - glycosylation - total synthesis - oligosaccharides

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1969-3992.
  • Supporting Information


Publication History

Received: 17 August 2022

Accepted after revision: 27 October 2022

Accepted Manuscript online:
27 October 2022

Article published online:
23 November 2022

© 2022. Thieme. All rights reserved

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  • References and Notes

  • 1 Varki A. Glycobiology 2017; 27: 3
    CrossrefPubMed
  • 2 Bertozzi CR, Kiessling LL. Science 2001; 291: 2357
    CrossrefPubMed
  • 3 Seeberger PH. Chem. Rev. 2021; 121: 3598
    CrossrefPubMed
  • 4 Crich D. J. Am. Chem. Soc. 2021; 143: 17
    CrossrefPubMed
  • 5 Krasnova L, Wong C.-H. J. Am. Chem. Soc. 2019; 141: 3735
    CrossrefPubMed
  • 6 Xiao G, Shao X, Zhu D, Yu B. Nat. Prod. Rep. 2019; 36: 769
    CrossrefPubMed
  • 7 Bennett CS, Galan MC. Chem. Rev. 2018; 118: 7931
    CrossrefPubMed
  • 8 Panza M, Pistorio SG, Stine KJ, Demchenko AV. Chem. Rev. 2018; 118: 8105
    CrossrefPubMed
  • 9 Leng W.-L, Yao H, He J.-X, Liu X.-W. Acc. Chem. Res. 2018; 51: 628
    CrossrefPubMed
  • 10 Peng P, Schmidt RR. Acc. Chem. Res. 2017; 50: 1171
    CrossrefPubMed
  • 11 Danishefsky SJ, Shue Y.-K, Chang MN, Wong C.-H. Acc. Chem. Res. 2015; 48: 643
    CrossrefPubMed
  • 12 Boltje TJ, Buskas T, Boons GJ. Nat. Chem. 2009; 1: 611
    CrossrefPubMed
  • 13 Zhu X, Schmidt RR. Angew. Chem. Int. Ed. 2009; 48: 1900
    CrossrefPubMed
  • 14 Ernst B, Magnani J. Nat. Rev. Drug Discovery 2009; 8: 661
    CrossrefPubMed
  • 15 Seeberger PH, Werz DB. Nature 2007; 446: 1046
    CrossrefPubMed
  • 16 Carbohydrate-Based Drug Discovery 2003
  • 17 Liu Y, Wang F. Carbohydr. Polym. 2007; 70: 386
    Crossref
    • 18a Kim G.-Y, Choi G.-S, Lee S.-H, Park Y.-M. J. Ethnopharmacol. 2004; 95: 69
      CrossrefPubMed
    • 18b Li G, Kim D.-H, Kim T.-D, Park B.-J, Park H.-D, Park J.-I, Na M.-K, Kim H.-C, Hong N.-D, Lim K, Hwang B.-D, Yoon W.-H. Cancer Lett. 2004; 216: 175
      CrossrefPubMed
  • 19 Kim D.-H, Yang B.-K, Jeong S.-C, Park J.-B, Cho S.-P, Das S, Yun J.-W, Song C.-H. Biotechnol. Lett. 2001; 23: 513
    CrossrefPubMed
  • 20 Ajith TA, Janardhanan KK. J. Ethnopharmacol. 2002; 81: 387
    CrossrefPubMed
  • 21 Kulkarni SS, Wang C.-C, Sabbavarapu NM, Podilapu AR, Liao P.-H, Hung S.-C. Chem. Rev. 2018; 118: 8025
    CrossrefPubMed
    • 22a Zhang Y, Hu Y, Liu S, He H, Sun R, Lu G, Xiao G. Chem. Sci. 2022; 13: 7755
      CrossrefPubMed
    • 22b Zhang Y, He H, Chen Z, Huang Y, Xiang G, Li P, Yang X, Lu G, Xiao G. Angew. Chem. Int. Ed. 2021; 60: 12597
      CrossrefPubMed
    • 22c He H, Xu L, Sun R, Zhang Y, Huang Y, Chen Z, Li P, Yang R, Xiao G. Chem. Sci. 2021; 12: 5143
      CrossrefPubMed
    • 22d Yang R, He H, Chen Z, Huang Y, Xiao G. Org. Lett. 2021; 23: 8257
      CrossrefPubMed
    • 22e Zhang Y, Chen Z, Huang Y, He S, Yang X, Wu Z, Wang X, Xiao G. Angew. Chem. Int. Ed. 2020; 59: 7576
      CrossrefPubMed
    • 22f Li P, He H, Zhang Y, Yang R, Xu L, Chen Z, Huang Y, Bao L, Xiao G. Nat. Commun. 2020; 11: 405
      CrossrefPubMed
    • 22g Zhang Y, Xiang G, He S, Hu Y, Liu Y, Xu L, Xiao G. Org. Lett. 2019; 21: 2335
      CrossrefPubMed
    • 22h Yang R, Sun X, Zhang Y, Xiao G. Org. Biomol. Chem. 2022; 20: 6755
      CrossrefPubMed
    • 23a Yu B, Sun J. Chem. Commun. 2010; 46: 4668
      CrossrefPubMed
    • 23b Yu B, Tao H. Tetrahedron Lett. 2001; 42: 2405
      Crossref
  • 25 Premathilake HD, Mydock LK, Demchenko AV. J. Org. Chem. 2010; 75: 1095
    CrossrefPubMed
  • 26 Tetrasaccharide 3; Typical ProcedureA solution of 10 (162.0 mg, 0.077 mmol) in 1:1 MeOH–CH2Cl2 (2 mL) was adjusted to pH 12 by the addition of NaOMe, and the mixture was stirred overnight at rt. The mixture was then neutralized to pH 7 with 1 M aq HCl, filtered, and concentrated. The residue was purified by column chromatography [Sephadex LH 20, MeOH–CH2Cl2 (1:1)] to give an intermediate; yield: 116.0 mg (89%).A mixture of the intermediate (50.0 mg, 0.029 mmol) and 10% Pd/C (316.8 mg) in EtOAc (3 mL)–MeOH (7 mL)–H2O (0.7 mL)–HOAc (0.07 mL) was stirred under H2 at rt for 2 d, then filtered and concentrated in vacuo. The residue was purified over a Sephadex TM LH-20 column (H2O) to give 3 as a white solid; yield: 18.6 mg (81%); [α]D 25 –18.93 (c 0.120, H2O).1H NMR (400 MHz, D2O): δ = 4.72 (d, J = 8.0 Hz, 1 H), 4.51 (dd, J = 8.0, 6.4 Hz, 2 H), 4.45 (d, J = 8.0 Hz, 1 H), 4.23–4.16 (m, 2 H), 3.94–3.80 (m, 5 H), 3.76–3.57 (m, 6 H), 3.53–3.22 (m, 13 H), 3.00 (t, J = 7.5 Hz, 2 H), 1.71–1.62 (m, 4 H), 1.47–1.39 (m, 2 H). 13C NMR (151 MHz, D2O): δ = 102.88, 102.78, 102.57, 102.16, 84.31, 75.96, 75.66, 75.52, 75.47, 74.85, 74.81, 73.40, 73.01, 72.96, 72.80, 70.14, 69.51, 69.38, 69.26, 68.73, 68.54, 68.07, 60.63, 60.59, 39.32, 28.14, 26.43, 25.08, 22.05. HRMS (ESI): m/z [M + H]+ calcd for C29H54NO21: 752.3183; found: 752.3191.Hexasaccharide 2Prepared from 7, and purified over a Sephadex LH-20 column (H2O) as a white solid; yield: 35 mg (86%); [α]D 25 –28.68 (c 0.08, H2O). 1H NMR (400 MHz, D2O): δ = 4.73 (d, J = 8.0 Hz, 1 H), 4.55–4.48 (m, 4 H), 4.45 (d, J = 8.0 Hz, 1 H), 4.24–4.16 (m, 4 H), 3.94–3.81 (m, 7 H), 3.77–3.56 (m, 9 H), 3.53–3.43 (m, 9 H), 3.43–3.21 (m, 9 H), 2.99 (t, J = 7.5 Hz, 2 H), 1.72–1.60 (m, 4 H), 1.49–1.40 (m, 2 H). 13C NMR (201 MHz, D2O): δ = 103.05, 102.88, 102.86, 102.81, 102.69, 102.19, 84.20, 75.98, 75.89, 75.70, 75.64, 75.56, 75.54, 75.50, 74.91, 74.87, 74.81, 74.57, 73.44, 73.06, 73.05, 73.03, 73.00, 72.83, 70.17, 69.60, 69.55, 69.44, 69.38, 69.37, 68.80, 68.74, 68.57, 68.52, 67.97, 60.69, 39.37, 28.18, 26.50, 23.24, 22.09, 20.07. HRMS (ESI): m/z [M + H]+ calcd for C41H74NO31: 1076.4239; found: 1076.4240.Nonasaccharide 1Prepared from 21, and purified over a Sephadex LH-20 column (H2O) as a white solid; yield: 29 mg (75%); [α]D 25 –43.78 (c 0.08, H2O). 1H NMR (400 MHz, D2O): δ = 4.64 (d, J = 8.0 Hz, 1 H), 4.44–4.37 (m, 7 H), 4.35 (d, J = 8.0 Hz, 1 H), 4.13–4.08 (m, 5 H), 3.88–3.66 (m, 13 H), 3.63–3.45 (m, 16 H), 3.41–3.10 (m, 22 H), 2.89 (t, J = 7.5 Hz, 2 H), 1.62–1.50 (m, 4 H), 1.39–1.29 (m, 2 H). 13C NMR (201 MHz, D2O): δ = 106.29, 106.27, 106.18, 106.10, 105.99, 105.82, 105.64, 105.49, 87.49, 81.81, 81.65, 79.28, 79.24, 78.99, 78.86, 78.83, 78.80, 78.73, 78.20, 78.19, 78.17, 78.11, 78.08, 78.03, 77.85, 77.46, 77.32, 76.73, 76.40, 76.34, 76.31, 76.29, 76.19, 76.12, 73.45, 72.85, 72.73, 72.71, 72.69, 72.67, 72.04, 71.93, 71.26, 71.11, 63.99, 63.83, 63.23, 63.15, 42.64, 31.47, 29.72, 28.28, 25.38. HRMS (ESI): m/z [M + H]+ calcd for C59H104NO46: 1562.5824; found: 1562.5826.