Dodecamannosylated Fullerenes as Escherichia coli ?· Dodecamannosylated Fullerenes as Escherichia coli…

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  • 1

    Supporting Information

    Dodecamannosylated Fullerenes as Escherichia coli FimH Ligands and Bacterial Antiadhesives

    Maxime Durka,a Kevin Buffet,a Julien Iehl,b Michel Holler,b

    Jean-Franois Nierengarten,*b Joemar Taganna,c Julie Bouckaert,*c

    Stphane P. Vincent*a

    a University of Namur (FUNDP), Dpartement de Chimie, Laboratoire de Chimie Bio-

    Organique, rue de Bruxelles 61, B-5000 Namur, Belgium; E-mail: stephane.vincent@fundp.ac.be

    b Laboratoire de Chimie des Matriaux Molculaires, Universit de Strasbourg et CNRS (UMR

    7509), Ecole Europenne de Chimie, Polymres et Matriaux (ECPM), 25 rue Becquerel, 67087

    Strasbourg Cedex 2 (France). E-mail: nierengarten@chimie.u-strasbg.fr

    c Structural Biology Brussels at the Vrije Universiteit Brussel Pleinlaan 2, 1050 Brussels

    (Belgium); E-mail: bouckaej@vub.ac.be

    Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2011

  • 2

    TABLE OF CONTENTS

    SYNTHESIS 3

    Experimental section 3

    Characterization of compound 3 13

    HAEMAGLUTINATION INHIBITION ASSAYS (HIA) 17

    ISOTHERMAL TITRATION CALORIMETRY (ITC) 19

    SURFACE PLASMON RESONANCE (SPR) 28

    NMR DATA 42

    MODEL STRUCTURE OF MANNOSYLATED FULLERENE IN INTERACTION WITH 6 FIMH MOLECULES 77

    Acknowledgements - We are grateful to Swaine Chen for strain UTI89, and to Mehdi Almant

    for the amide-functionalised heptyl mannoside.

    Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2011

  • 3

    SYNTHESIS

    Experimental Section

    General. Reagents and solvents were purchased as reagent grade and used without further

    purification. Compounds 1,1 2,1 18,2 231,3 and 241,4 were prepared according to previously

    reported procedures. All reactions were performed in standard glassware under an inert Ar or N2

    atmosphere. Microwave irradiation reaction was performed in a Biotage Initiator. Evaporation

    and concentration were done at water aspirator pressure and drying in vacuo at 10-2 Torr. Column

    chromatography: silica gel 60 (230-400 mesh, 0.040-0.063 mm) was purchased from E. Merck.

    Thin Layer Chromatography (TLC) was performed on glass or aluminium sheets coated with

    silica gel 60 F254 purchased from E. Merck, visualization by UV light or by revelation with

    ethanolic phosphomolybdic acid. IR spectra (cm-1) were measured on an ATI Mattson Genesis

    Series FTIR instrument. NMR spectra were recorded on a Bruker AC 300, AC 400 or JEOL ECX

    400 with solvent peaks as reference. Compounds were characterized by 1H, 13C, and NMR as

    well as by 1H-1H correlation and 1H-13C experiments when necessary. All The following

    abbreviations were used to describe the multiplicities: s=singlet, d=doublet, t=triplet,

    m=multiplet, quint.=quintuplet br s=broad singlet.

    1 J.-F. Nierengarten, J. Iehl, V. Oerthel, M. Holler, B. M. Illescas, A. Muoz, N. Martn, J. Rojo, M. Snchez-Navarro, S. Cecioni, S. Vidal, K. Buffet, M. Durka, S. P. Vincent, Chem. Commun. 2010, 46, 3860. 2 J. Iehl and J.-F. Nierengarten, Chem. Eur. J. 2009, 15, 7306. 3 R. J. Kaufman and R. S. Sidhu et al. J. Org. Chem. 1982, 47, 4941; M. Touaibia, A. Wellens, T. C. Shiao, Q. Wang, S. Sirois, J. Bouckaert and R. Roy, ChemMedChem, 2007, 2, 1190; P. van der Peet, C. T. Gannon, I. Walker, Z. Dinev, M. Angelin, S. Tam, J. E. Ralton, M. J. McConville and S. J. Williams, ChemBioChem 2006, 7, 1384; . Ferrandiz-Huertas, J. Isac-Garca, F. Prez-Balderas and F. Santoyo-Gonzlez, Synthesis 2005, 6, 939. 4 Y. Yamada, K. Matsuura and K. Kobayashi, Bioorg. Med. Chem. 2005, 13, 1913.

    Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2011

  • 4

    Compound 4

    22

    CuI / DIEA / DMF

    (35%)

    OHO

    HO

    OHOH

    O

    OHO

    HO

    OHOH

    ON

    NN

    OO

    23 4

    H

    N3 O

    O

    A solution of 23 (22 mg, 0.1 mmol, 1 eq.), 22 (18 mg, 0.12 mmol, 1.2 eq.), DIEA5 (41.8 L, 0.24

    mmol, 2 eq.) and CuI (9.5 mg, 0.05 mmol, 0.5 eq.) in dry DMF (200.0 L) was warmed to 80C

    under microwave irradiation during 1 hour. The solvents were then evaporated under reduced

    pressure. Column chromatography (SiO2, EtOAc to EtOAc/EtOH 8:2) gave 4 (14 mg, 35%) as a

    yellow oil. []D20 (MeOH, c = 0.5) = +26.2. 1H NMR (21.1C, 400 MHz, D2O) = 7.95 (s,1 H),

    4.82 (d, J = 1.4 Hz, 1 H), 4.62 (AB, J =12.4 Hz, 2 H), 4.43 (t, J = 6.4 Hz, 2 H), 3.97 (t, J = 5.5

    Hz, 2 H), 3.78 (dd, J = 1.6 and 3.2 Hz, 1 H), 3.71 (m, 1 H), 3.64-3.58 (m, 1 H), 3.62 (m, 1 H),

    3.52 (t, J = 9.9 Hz, 1 H), 3.54-3.48 (m, 1 H), 2.17 (quint., J = 5.9 Hz, 2 H), 0.95 (s, 9 H). 13C

    NMR (21.6C, 101 MHz, D2O) = 181.8, 125.4, 99.5, 72.9, 70.5, 69.9, 66.7, 62.6, 60.8, 59.7,

    48.1, 38.5, 28.2, 26.18. MS (TOF-MS-ES+): m/z: 242.15 (100%, [M-C6H11O6+NH4]+), 404.2041

    (88%, [M+H]+). HRMS: calcd for C17H30N3O8, [M+H]+: 404.2027, found: 404.2041.

    Compound 5

    22

    CuI / DIEA / DMF

    (58%)

    OHOHO

    OHOH

    O

    OHOHO

    OHOH

    ON

    NN

    O

    O

    24 5

    H

    4 4

    The same procedure described for compound 4 was applied with 24 (15 mg, 0.058 mmol, 1 eq.),

    22 (12 mg, 0.069 mol, 1.2 eq.), DIEA (20.0 L, 0.115 mmol, 2 eq.) and CuI (5.0 mg, 0.0262

    5 DIEA : Diisopropyl Ethylamine

    Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2011

  • 5

    mmol, 0.5 eq.) in dry DMF (120 L). The solution was warmed to 80C under microwave

    irradiation during 1 hour. The solvents were then evaporated under reduced pressure. Column

    chromatography (SiO2, EtOAc to EtOAc/EtOH 9:1) gave 5 (15 mg, 58%) as a yellow oil. []D20

    (MeOH, c = 0.2) = +4.7. 1H NMR (21.8C, 400 MHz, D2O) = 7.73 (s,1 H), 4.74 (s, 1 H), 4.29

    (t, J = 6.2 Hz, 2 H), 3.99 (t, J = 5.5 Hz, 2 H), 3.82 (m, 1 H), 3.75 (d, J = 11.9 Hz, 1 H), 3.69-3.62

    (m, 3 H), 3.57-3.43 (m, 3 H), 2.65 (t, J = 7.1 Hz, 2 H), 2.20 (m, 2 H), 1.67-1.51 (m, 4 H), 1.00 (s,

    9 H). 13C NMR (22.0C, 101 MHz, D2O) = 181.7, 99.7, 72.7, 70.6, 70.1, 67.4, 66.7, 62.6, 60.9,

    48.0, 38.5, 28.2, 27.9, 26.2, 25.2, 24.3. MS (TOF-MS-ES+): m/z: 468.23 (100%, [M+Na]+),

    913.47 (21%, [2M+Na]+). HRMS: calcd for C20H35N3O8Na, [M+Na]+: 468.2316, found:

    468.2292. Rf = 0.16 (EtOAc/EtOH).

    Compound 6

    20

    CuI / DIEA / DMF

    (67%)

    13O

    HOHO

    OHOH

    O

    NH

    O

    N

    N N

    O

    O

    6

    A solution of 13 (67 mg, 0.15 mmol, 1 eq.), 20 (see structure below, 63 mg, 0.37 mmol, 2.5 eq.),

    DIEA (52 L, 0.30 mmol, 2 eq.) and CuI (3 mg, 0.015 mmol, 0.5eq.) in dry DMF (2 mL) was

    stirred 24 hours at room temperature. The solvents were then evaporated under reduced pressure.

    Column chromatography (SiO2, EtOAc to EtOAc/EtOH 85/15) gave 6 (41mg, 67%) as a yellow

    oil. []D20 (MeOH, c = 1.2) = 20.2. 1H NMR (19.7C, 400 MHz, CD3OD) = 7.74 (s, 1 H), 7.36

    (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), 4.81 (d, J = 1.6 Hz, 1 H), 4.61 (AB, J = 12.4 Hz, 2

    H), 4.37 (t, J = 7.1 Hz, 2 H), 4.15 (s, 2 H), 4.07 (t, J = 6.4 Hz, 2 H), 3.82 (m, 1 H), 3.81 (dd, J =

    1.8 and 3.4 Hz, 1 H), 3.70 (dd, J = 3.9 and 9.4Hz, 1 H), 3.67 (m, 1 H), 3.60 (br t, J = 9.9 Hz, 1

    H), 3.54 (ddd, J = 2.3, 5.7 and 9.9 Hz, 1 H), 2.74 (t, J = 7.8 Hz, 2 H), 2.26 (t, J = 7.3 Hz, 2 H),

    2.00-1.88 (m, 4 H), 1.61 (quint., J = 7.6 Hz, 2 H), 1.17 (s, 9 H). 13C NMR (22C, 100 MHz,

    CD3OD) = 178.7, 173.8, 138.2, 131.3, 127.7, 122.2, 99.5, 84.9, 81.8, 73.7, 71.3, 70.8, 68.0,

    67.3, 63.4, 61.6, 49.6, 34.6, 29.4, 28.9, 28.2, 26.2, 22.3, 21.6. MS (TOF-MS-ES+): m/z: 617.32

    (100%, [M+H]+), 639.30 (100%, [M+Na]+). HRMS: calcd for C31H45N4O9, [M+H]+: 617.3181,

    found: 617.3189. Rf = 0.23 (EtOAc/EtOH 8:2).

    Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2011

  • 6

    Compound 8

    A solution of 14 (5.93 mL, 92.40 mmol, 2 eq.) and 15 (4.63 mL, 46.20 mmol, 1 eq.) in dry THF

    (30.0 mL) was heated under reflux for 3 days. The solvent was evaporated under reduced

    pressure. Column chromatography (SiO2, EtOAc/MeOH 85:15) afforded 8 (6.48 g, 90%) as a

    yellow solid. 1H NMR (21.8C, 400 MHz, CDCl3) = 5.74 (bs, 1 H), 4.05 (dd, J = 2.5 Hz, J =

    5.3 Hz, 2 H), 3.65 (q, J = 6.0 Hz, 2 H), 2.26 (t, J = 7.1 Hz, 2 H), 2.23 (t, J = 2.5 Hz, 1 H), 1.76

    (m, 3 H), 1.60 (m, 2 H). 13C NMR (22.0C, 101 MHz, CDCl3) = 172.9, 79.7, 71.7, 62.2, 35.8,

    31.9, 29.3, 21.7. MS (TOF-MS-ES+): m/z: 178.0835 (100%, [M+Na]+), 278.1318 (32%,

    [M+C5H8O2+Na]+). HRMS-ESI: calcd for C8H13NO2Na

    + [M+Na]+: 178.0838, found: 178.0835.

    Rf = 0.4 (EtOAc/MeOH 9:1).

    Compound 9

    Alcohol 17 (5.12 g, 21.80 mmol, 1.7 eq.) and BF3.Et2O (8.11 mL, 64.00 mmol, 5 eq.) were added

    dropwise to a solution of 16 (5.00 g, 12.80 mmol, 1 eq.) in dry CH2Cl2 (100.0 mL) at 0C under

    an argon atmosphere. The mixture was allowed to warm to room temperature and stirred at this

    temperature for 24 hours. The solution was then washed with a saturated aqueous NaHCO3

    solution (2x 100 mL), then water (100 mL). The aqueous phase was extracted with CH2Cl2 (3 x

    100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated.

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