Synlett 2017; 28(20): 2807-2811
DOI: 10.1055/s-0036-1590884
letter
© Georg Thieme Verlag Stuttgart · New York

New Triazole-Containing Branched Bis(dipeptidomimetic) – Switching from Self-Dimerization to Anion-Binding Properties

Tin-Ki Chui, Hak-Fun Chow*
  • Department of Chemistry and Institute of Molecular Functional Materials, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR   Email: hfchow@cuhk.edu.hk
This work is supported by the UGC of HK (project no: AoE/P-03/08). The 700 MHz NMR spectrometer was funded by the UGC of HKSAR (SEG/CUHK09).
Further Information

Publication History

Received: 30 June 2017

Accepted after revision: 28 July 2017

Publication Date:
25 August 2017 (eFirst)

Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

A triazole-containing branched bis(dipeptidomimetic) 2 using l-lysine as a flexible branching unit was synthesized and characterized. The compound was found to form weak dimers (K dim = 19 M–1) in chloroform as shown by vapor pressure osmometry (VPO) and concentration-dependent 1H NMR studies. On the other hand, the compound was capable of binding chloride and monobasic diethyl phosphate (DEP) in chloroform. Job plot analysis, MALDI-TOF mass spectrometry, and NMR titration studies revealed a 1:1 binding stoichiometry with good binding affinities (K a ≈ 640–780 M–1). Structural studies using ­ROESY NMR spectroscopy and molecular modelling on the 2–DEP complex indicated the adoption of a helix-like conformation by the host with the guest situated near the branching juncture.

Supporting Information

 
  • References and Notes

  • 1 Wynn JE. Santos WL. Org. Biomol. Chem. 2015; 13: 5848
    • 2a Scully CC. G. Jensen P. Rutledge PJ. J. Organomet. Chem. 2008; 693: 2869
    • 2b Szyrwiel Ł. Szczukowski Ł. Pap JS. Setner B. Szewczuk Z. Malinka W. Inorg. Chem. 2014; 53: 7951
    • 2c Lakatos A. Gyurcsik B. Nagy NV. Csendes Z. Wéber E. Fülöp L. Kiss T. Dalton Trans. 2012; 41: 1713
  • 3 Pap J. Szyrwiel Ł. Srankó D. Kerner Z. Setner B. Szewczuk Z. Malinka W. Chem. Commun. 2015; 51: 6322
    • 4a Boyce R. Li G. Nestler P. Suenaga T. Still WC. J. Am. Chem. Soc. 1994; 116: 7955
    • 4b Davies M. Bonnat M. Guillier F. Kilburn JD. Bradley M. J. Org. Chem. 1998; 63: 8696
    • 4c Conza M. Wennemers H. J. Org. Chem. 2002; 67: 2696
    • 5a Schneider SE. O’Neil SN. Anslyn EV. J. Am. Chem. Soc. 2000; 122: 542
    • 5b Kuchelmeister HY. Karczewski S. Gutschmidt A. Knauer S. Schmuck C. Angew. Chem. Int. Ed. 2013; 52: 14016
  • 6 Wennemers H. Chimia 2003; 57: 237
  • 7 Ryadnov MG. Woolfson DN. Angew. Chem. Int. Ed. 2003; 42: 3021
  • 8 Gudlur S. Sukthankar P. Gao J. Avila LA. Hiromasa Y. Chen J. Iwamoto T. Tomich JM. PLoS One 2012; 7: e45374
  • 9 Hanessian S. Vinci V. Fettis K. Maris T. Phan Viet MT. J. Org. Chem. 2008; 73: 1181
  • 10 For a review of peptide bond isosteres, see: Choudhary A. Raines RT. ChemBioChem 2011; 12: 1801
  • 11 Lauria A. Delisi R. Mingoia F. Terenzi A. Martorana A. Barone G. Almerico AM. Eur. J. Org. Chem. 2014; 3289
  • 12 Ramírez MA. Martín VS. Gallardo AG. Comput. Theor. Chem. 2013; 1026: 31
    • 13a Horne WS. Stout CD. Ghadiri MR. J. Am. Chem. Soc. 2003; 125: 9372
    • 13b Horne WS. Yadav MK. Stout CD. Ghadiri MR. J. Am. Chem. Soc. 2004; 126: 15366
    • 13c Qin S.-Y. Xu X.-D. Chen C.-S. Chen J.-X. Li Z.-Y. Zhuo R.-X. Zhang X.-Z. Macromol. Rapid Commun. 2011; 32: 758
  • 14 Zhan J. Tian D. Li H. New J. Chem. 2009; 33: 725
    • 15a Li Y. Flood AH. Angew. Chem. Int. Ed. 2008; 47: 2649
    • 15b Hua Y. Flood AH. Chem. Soc. Rev. 2010; 39: 1262
    • 15c Yim S.-L. Chow H.-F. Chan M.-C. Chem. Commun. 2014; 50: 3064
    • 15d Flood AH. Beilstein J. Org. Chem. 2016; 12: 611
  • 16 You L.-Y. Chen S.-G. Zhao X. Liu Y. Lan W.-X. Zhang Y. Lu H.-J. Cao C.-Y. Li Z.-T. Angew. Chem. Int. Ed. 2012; 51: 1657
    • 17a Chow H.-F. Lau K.-N. Ke Z. Liang Y. Lo C.-M. Chem. Commun. 2010; 3437
    • 17b Chow H.-F. Lo C.-M. Chen Y. Top. Heterocycl. Chem. 2012; 28: 137
    • 17c Chow H.-F. Chui T.-K. Qi Q. Synlett 2014; 25: 2246
  • 18 Ke Z. Chow H.-F. Chan M.-C. Liu Z. Sze K.-H. Org, Lett. 2012; 14: 394
  • 19 Chow H.-F. Ng K.-F. Wang Z.-Y. Wong C.-H. Luk T. Lo C.-M. Yang Y.-Y. Org. Lett. 2006; 8: 471
  • 20 See Supporting Information for details.
  • 21 Typical Experimental Procedure – Compound 2 Boc-V-Prg (56 mg, 0.22 mmol) and diazide 7 (57 mg, 0.1 mmol) were dissolved in degassed THF. CuSO4·5H2O (5.5 mg, 22 μmol) and sodium ascorbate (22 mg, 0.11 mmol) were then added, followed by the addition of small amount of water. The reaction mixture was stirred at 25 °C for 12 h. Saturated KHSO4 aqueous solution was added to quench the reaction. THF was removed under reduced pressure, and the remaining slurry aqueous layer was extracted with EtOAc. The organic extracts were then combined, washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (hexane/EtOAc = 1:1) to afford the product 2 (76 mg, 0.07 mmol, 71%) as a white solid; 159–162 °C; Rf = 0.38 (EtOAc). 1H NMR (400 MHz, CDCl3): δ = 8.01 (s, T′, 1 H), 7.96 (s, T, 1 H), 7.71 (br d, J = 7.5, LαNH, 1 H), 7.46 (br s, NH2 and NH2′, 2 H), 7.39 (br s, LεNH, 1 H), 5.49 (br d, J = 8.7, BocNH or BocNH′, 1 H), 5.44 (br d, J = 8.8, BocNH′ or BocNH, 1 H), 5.16 (d, J = 10.2, V1αCH, 1 H), 4.95 (d, J = 10.2, V1′αCH, 1 H), 4.65–4.47 (m, CH2Triaz and LαCH, 5 H), 4.20–4.10 (m, V2αCH and V2′αCH, 2 H), 4.07–3.97 (m, OCH2, 2 H), 3.30–3.19 (m, LεCHH, 1 H), 3.15–3.05 (m, LεCHH, 1 H), 2.60–2.45 (m, 2 H), 2.17–2.04 (m, 2 H), 1.80–1.70 (m, 1 H), 1.64–1.50 (m, 3 H), 1.50–1.44 (m, 3 H), 1.40 (s, C(CH3)3, 18 H), 1.35–1.26 (m, 6 H), 1.20–1.10 (m, 4 H), 1.11 (d, J = 6.4, CH3, 3 H), 1.05 (d, J = 6.4, CH3, 6 H), 0.94–0.85 (m, CH3, 21 H), 0.77 (d, J = 6.4, CH3, 3 H), 0.76 (d, J = 6.4, CH3, 3 H). 13C NMR (100 MHz, CDCl3): δ = 172.3, 172.2, 171.8, 168.3, 168.2, 156.2, 144.6, 122.2, 122.0, 79.5, 70.1, 69.6, 68.1, 59.6, 52.3, 38.9, 37.6, 35.8, 35.7, 34.9, 32.2, 32.0, 31.5, 31.0, 28.7, 28.6, 28.3, 28.2, 22.6, 19.24, 19.16, 18.7, 18.0, 17.9; [α] –7.4 (c 0.06, CHCl3); ESI-MS: m/z (%) = 1096 (100) [M + Na+]. ESI-HRMS: m/z calcd for C54H96N12O10 + Na+: 1095.7265; found: 1095.7297.
  • 22 Baxter NJ. Williamson MP. Lilley TH. Haslam E. J. Chem. Soc., Faraday Trans. 1996; 92: 231
  • 23 Wang Y. Xiang J. Jiang H. Chem. Eur. J. 2011; 17: 613
  • 24 MacroModel, Version 10.9 . Schrödinger, LLC; New York, NY; 2015
  • 25 Jaguar, Version 9.3 . Schrödinger, LLC; New York, NY; 2016