Download PDF
Synlett 2018; 29(07): 904-907
DOI: 10.1055/s-0036-1591902
letter
© Georg Thieme Verlag Stuttgart · New York

Glycosylated α-Azido Amino Acids: Versatile Intermediates in the Synthesis of Neoglycoconjugates

Róisín O’Flaherty 
a   Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland   Email: trinidad.velascotorrijos@mu.ie
b   NIBRT GlycoScience Group, NIBRT - The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland
,
Trinidad Velasco-Torrijos  *
a   Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland   Email: trinidad.velascotorrijos@mu.ie
› Author AffiliationsThe authors want to thank the Irish Research Council (IRC-IRCSET) for the award of a Postgraduate Scholarship to Róisín O’Flaherty.
Further Information

Publication History

Received: 05 November 2017

Accepted after revision: 21 December 2017

Publication Date:
06 February 2018 (online)

    Permissions and Reprints All articles of this category


Abstract

A series of glycosylated α-azido amino acids was synthesized as precursors for neoglycoconjugates, a class of important biomolecules for drug discovery, and sensor development. The synthetically challenging 1,2-cis α-galactosylated species described herein were designed as building blocks in the synthesis of analogues of α-galactosyl ceramide, a potent immunomodulator. A benzyl-protected 1,2,3-triazolyl α-galactosyl-l-serine derivative was prepared using copper azide alkyne cycloaddition to showcase the potential of glycosylated α-azido amino acids in neoglycoconjugate design.

Key words

α-azido amino acid - glycosylation - neoglycoconjugates 1,2,3-triazolyl glycosides - CuAAC reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591902.
  • Supporting Information
 

  • References and Notes

  • 1 Meldal M. Tornøe CW. Chem. Rev. 2008; 108: 2952
    CrossrefPubMed
  • 2 Maruani A. Richards DA. Chudasama V. Org. Biomol. Chem. 2016; 14: 6165
    CrossrefPubMed
  • 3 Tang W. Becker ML. Chem. Soc. Rev. 2014; 43: 7013
    CrossrefPubMed
  • 4 Hein JE. Fokin VV. Chem. Soc. Rev. 2010; 39: 1302
    CrossrefPubMed
    • 5a Tiwari VK. Mishra BB. Mishra KB. Mishra N. Singh AS. Chen X. Chem. Rev. 2016; 116: 3086
      CrossrefPubMed
    • 5b McKay CS. Finn MG. Chem. Biol. 2014; 21: 1075
      CrossrefPubMed
  • 6 Leyden R. Murphy P. Synlett 2009; 1949
    Article in Thieme Connect
  • 7 Campo VL. Marchiori MF. Rodrigues LC. Dias-Baruffi M. Glycoconjugate J. 2016; 33: 853
    CrossrefPubMed
  • 8 He XP. Zeng YL. Zang Y. Li J. Field RA. Chen GR. Carbohydr. Res. 2016; 429: 1
    CrossrefPubMed
  • 9 Lim D. Brimble MA. Kowalczyk R. Watson AJ. A. Fairbanks AJ. Angew. Chem. Int. Ed. 2014; 53: 11907
    CrossrefPubMed
  • 10 Gunther KU. Ziegler T. Synthesis 2014; 46: 2362
    Article in Thieme Connect
  • 11 Herzner H. Reipen T. Schultz M. Kunz H. Chem. Rev. 2000; 100: 4495
    CrossrefPubMed
  • 12 Brocke C. Kunz H. Bioorg. Med. Chem. 2002; 10: 3085
    CrossrefPubMed
  • 13 Hojo H. Nakahara Y. Curr. Protein Pept. Sci. 2000; 1: 23
    CrossrefPubMed
  • 14 Halkes KM. St Hilaire PM. Jansson AM. Gotfredsen CH. Meldal M. J. Chem. Soc., Perkin Trans. 1 2000; 2127
  • 15 Manabe S. Sakamoto K. Nakahara Y. Sisido M. Hohsaka T. Ito Y. Bioorg. Med. Chem. 2002; 10: 573
    CrossrefPubMed
  • 16 Baker A. Turner NJ. Webberley MC. Tetrahedron: Asymmetry 1994; 5: 2517
    Crossref
  • 17 Polakova M. Pitt N. Tosin M. Murphy PV. Angew. Chem. Int. Ed. 2004; 43: 2518
    CrossrefPubMed
  • 18 Carreno LJ. Kharkwal SS. Porcelli SA. Immunotherapy 2014; 6: 309
    CrossrefPubMed
  • 19 Marzabadi CH. Franck RW. Chem. Eur. J. 2016; 22: 1
    Crossref
  • 20 Laurent X. Bertin B. Renault N. Farce A. Speca S. Milhomme O. Millet R. Desreumaux P. Hénon E. Chavatte P. J. Med. Chem. 2014; 57: 5489
    CrossrefPubMed
  • 21 Anderson B. Teyton L. Bendelac A. Savage P. Molecules 2013; 18: 15662
    CrossrefPubMed
  • 22 Lee T. Cho M. Ko SY. Youn HJ. Baek DJ. Cho WJ. Kang CY. Kim S. J. Med. Chem. 2007; 50: 585
    CrossrefPubMed
  • 23 Verma YK. Reddy BS. Pawar MS. Bhunia D. Sampath Kumar HM. ACS Med. Chem. Lett. 2016; 7: 172
    CrossrefPubMed
  • 24 Jervis PJ. Graham LM. Foster EL. Cox LR. Porcelli SA. Besra GS. Bioorg. Med. Chem. Lett. 2012; 22: 4348
    CrossrefPubMed
  • 25 Ramanathan SK. Keeler J. Lee HL. Reddy DS. Lushington G. Aubé J. Org. Lett. 2005; 7: 1059
    CrossrefPubMed
  • 26 Sowinski JA. Toogood PL. J. Org. Chem. 1996; 61: 7671
    CrossrefPubMed
  • 27 Zaloom J. Roberts DC. J. Org. Chem. 1981; 46: 5173
    Crossref
  • 28 Nyffeler PT. Liang CH. Koeller KM. Wong CH. J. Am. Chem. Soc. 2002; 124: 10773
    CrossrefPubMed
  • 29 Goddard-Borger ED. Stick RV. Org. Lett. 2007; 9: 3797
    CrossrefPubMed
  • 30 Antoon JW. Liu J. Gestaut MM. Burow ME. Beckman BS. Foroozesh M. J. Med. Chem. 2009; 52: 5748
    CrossrefPubMed
  • 31 Marine JE. Liang X. Song S. Rudick JG. J. Pept. Sci. 2015; 104: 419
    CrossrefPubMed
  • 32 Garegg J. Hultberg H. Lindberg C. Carbohydr. Res. 1980; 83: 157
    Crossref
  • 33 Li ZT. Zhu LS. Kalikanda J. Tetrahedron Lett. 2011; 52: 5629
    Crossref
  • 34 Manabe S. Ueki A. Ito Y. Tetrahedron Lett. 2008; 49: 5159
    Crossref
  • 35 Weissman SA. Zewge D. Tetrahedron 2005; 61: 7833
    Crossref
  • 36 Representative Procedure for Glycosylation of α-Azido Amino Acid Derivatives NIS (276 mg, 1.23 mmol) was added to a solution of thiophenyl-2,3,4,6-tetra-O-benzyl-β-d-galactopyranoside (4, 388 mg, 0.61 mmol) and α-azido-l -serine tetradecyl amide (3c, 200 mg, 0.61 mmol) in anhydrous THF (6 mL) in the dark under N2and at rt. TfOH (2 μL) was added, and the reaction mixture was stirred for 20 h. MeOH was added, and the solvent was removed in the rotary evaporator. The residue was diluted with CH2Cl2 (20 mL) and washed with 1 M aq Na2S2O4 (20 mL) followed by brine (20 mL). The organic layer was dried (Na2SO4), filtered, and concentrated to give a brown solid (α/β anomeric ratio of 2.7:1 was estimated from integration of 1H NMR spectrum signals). The crude product was purified by flash column chromatography (PE to PE/EtOAc 5:1). Fractions containing glycosylated products 2α/2β were recovered in a combined yield of 328 mg, 63%. The α-anomer product 2α could be isolated as a white solid (81 mg, 35%): Rf = 0.13 (PE/EtOAc/toluene = 3:1:6); [α]D 25 +34.3 (c, 0.35 in CH2Cl2). IR (NaCl plate, CH2Cl2): νmax = 3350.5, 2924.3, 2858.2, 2108.2, 1726.4, 1452.2, 1261.4 cm–1. 1H NMR (300 MHz): δ = 0.87 (t, J = 7.3 Hz, 3 H, CH3), 1.25 (br s, 20 H, (CH 2)10CH3), 1.37–1.44 (m, 2 H, NHCH2 CH2(CH2)10CH3), 2.95–3.07 (m, 1 H, NHCH), 3.16–3.23 (m, 1 H, NHCH), 3.52–3.54 (m,2 H, H-6, H-6′), 3.68–3.76 (m, 1 H, H-β′), 3.90–3.96 (m, 3 H, H-3, H-4, H-5), 4.04–4.13 (m, 3 H, H-α, H-β, H-2), 4.38–4.95 (m, 8 H, CH2Ph × 4), 4.87 (d, J = 3.1 Hz, 1 H, H-1), 6.59 (t, J = 5.0 Hz, 1 H, NH), 7.26–7.36 (m, 20 H, aromatics). 13C NMR (75 MHz): δ = 14.1 (CH3), 26.9, 29.3, 29.40, 29.45, 29.5, 29.63, 29.67, 29.7, 31.9 (NHCH2(CH2)12CH3), 39.5 (NHCH2(CH2)12CH3), 63.0 (C-α), 68.8 (C-6), 69.1 (C-β), 70.0 (C-4 or C-5), 73.1, 73.5, 74.7, 74.8, (CH2Ph × 4), 74.9 (C-4 or C-5), 75.1 (C-2), 78.8 (C-3), 98.9 (C-1), 127.3, 127.4, 127.5, 127.6, 127.74, 127.76, 127.8, 127.9, 128.0, 128.23, 128.26, 128.32, 128.39, 128.4, 137.9, 138.4, 138.5, 138.6 (aromatics), 166.9 (CO). HRMS (ESI+): m/z calcd for C51H68N4O7H [M + H]+: 849.519; found: 849.5161.
  • 37 Mishra A. Tiwari VK. J. Org. Chem. 2015; 80: 4869
    CrossrefPubMed
  • 38 Thirumurugan P. Matosiuk D. Jozwiak K. Chem. Rev. 2013; 113: 4905
    CrossrefPubMed
  • 39 Xie J. Bogliotti N. Chem. Rev. 2014; 114: 7678
    CrossrefPubMed
  • 40 Pietrzik N. Schmollinger D. Ziegler T. Beilstein J. Org. Chem. 2008; 4: 30
    PubMed
    • 41a Campo VL. Carvalho I. Da Silva CH. T. P. Schenkman S. Hill L. Nepogodiev SA. Field RA. Chem. Sci. 2010; 1: 507
      Crossref
    • 41b Campo VL. Ivanova IM. Carvalho I. Lopes CD. Carneiro ZA. Saalbach G. Schenkman S. da Silva JS. Nepogodiev SA. Field RA. Tetrahedron 2015; 71: 7344
      CrossrefPubMed