Synlett 2013; 24(14): 1830-1834
DOI: 10.1055/s-0033-1339338
letter
© Georg Thieme Verlag Stuttgart · New York

Gentiobiosylation of β-Resorcylic Acid Esters and Lactones: First Synthesis and Characterization of Zearalenone-14-β,d-Gentiobioside

Julia Weber
a  Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria   Fax: +43(1)5880116399   Email: [email protected]
,
Hannes Mikula*
a  Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria   Fax: +43(1)5880116399   Email: [email protected]
,
Philipp Fruhmann
a  Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria   Fax: +43(1)5880116399   Email: [email protected]
,
Christian Hametner
a  Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria   Fax: +43(1)5880116399   Email: [email protected]
,
Elisabeth Varga
b  Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria
,
Franz Berthiller
b  Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria
,
Rudolf Krska
b  Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria
,
Johannes Fröhlich
a  Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria   Fax: +43(1)5880116399   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 25 May 2013

Accepted: 10 June 2013

Publication Date:
30 July 2013 (online)


Abstract

The development of an optimized protocol for the gen­tiobiosylation of β-resorcylic acid esters and lactones (β-RAL) is presented. Different gentiobiosyl donors were prepared and used for regioselective and diastereoselective glycosylation affording a reliable synthetic strategy towards this class of natural product glycosides. The improved procedure was finally used for the preparation of the masked Fusarium mycotoxin zearalenone-14-β,d-gentiobioside.

Supporting Information

 
  • References and Notes

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  • 19 Procedure for the Lewis Acid Mediated Synthesis of β-Gentiobiose Octaacetate (6) 1,2,3,4-Tetra-O-acetyl-β,d-glucose (4, 3.8 g, 11 mmol) and trichloroacetimidoyl donor 5 (5.8 g, 11.8 mmol) were dissolved in dry CH2Cl2 (100 mL). MS 3 Å (10 g) was added, and the mixture was stirred at r.t. under argon for 1 h. After cooling to –40 °C, TMSOTf (0.2 mL, 1.1 mmol) was added, and the reaction mixture was stirred at –40 °C for 16 h. The reaction was quenched by addition of Et3N, filtered through Celite, and concentrated. The crude product was purified by column chromatography (hexanes–EtOAc, 5:1 to 1:1) to obtain 6 (3.1 g, 43%) as a white solid. Analytical data matched those reported in the literature.22
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  • 24 Procedure for Anomeric Deprotection of 6 To a solution of 6 (1.31 g, 1.9 mmol) in dry THF (45 mL) was added benzylamine (0.23 mL, 2.1 mmol), and the reaction mixture was stirred at r.t. for 48 h. The solvent was removed under reduced pressure, and the residue was dissolved in CH2Cl2 (100 mL), washed with 1 M HCl (2 × 100 mL) and H2O (100 mL). The organic layer was dried over Na2SO4 and concentrated. Column chromatography (hexanes–EtOAc, 1:1 to 1:3) afforded the desired product 8 (0.91 g, 76%) as a white solid. Analytical data matched those reported in the literature.25
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  • 27 Procedure for the Synthesis of Gentiobiosyl Acetimidate Donor 10 To a solution of gentiobiose heptaacetate (8, 0.8 g, 1.3 mmol) in dry CH2Cl2 (20 mL) was added K2CO3 (0.36 g, 2.6 mmol) and N-phenyl-2,2,2-trifluoroacetimidoyl chloride (9, 0.4 mL, 2.6 mmol). The reaction mixture was stirred at r.t. and under argon for 24 h. The solvent was removed on a rotary evaporator, and the residue was purified by column chromatography (hexanes–EtOAc, 3:1) to yield 10 (0.82 g, 78%) as a white solid. Analytical Data for 10 1H NMR (200 MHz, CDCl3): δ = 7.39–7.22 (m, 2 H), 7.18–7.06 (m, 1 H), 6.86 (d, J = 7.6 Hz, 2 H), 5.77 (br s, 1 H), 5.25–5.15 (m, 2 H), 5.11 (d, J = 10.3 Hz, 1 H), 5.05–4.92 (m, 3 H), 4.56 (d, J = 7.8 Hz, 1 H), 4.25 (dd, J = 12.3, 4.7 Hz, 1 H), 4.12 (dd, J = 12.3, 2.3 Hz, 1 H), 3.90 (d, J = 9.4 Hz, 1 H), 3.76–3.56 (m, 3 H), 2.08 (s, 3 H), 2.06 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H), 2.01 (s, 3 H), 2.00 (s, 3 H), 1.95 (s, 3 H). 13C NMR (50 MHz, CDCl3): δ = 170.8 (s, 1 C), 170.3 (s, 1 C), 170.27 (s, 1 C), 169.6 (s, 1 C), 169.52 (s, 1 C), 169.49 (s, 1 C), 169.1 (s, 1 C), 142.9 (s, 1 C), 128.8 (d, 2 C), 124.6 (d, 1 C), 119.2 (d, 2 C), 100.5 (d, 1 C), 94.3 (d, 1 C), 74.1 (d, 1 C), 72.6 (d, 1 C), 72.4 (d, 1 C), 71.9 (d, 1 C), 70.8 (d, 1 C), 70.2 (d, 1 C), 68.3 (d, 1 C), 68.2 (d, 1 C), 67.3 (t, 1 C), 61.7 (t, 1 C), 20.9 (q, 1 C), 20.7 (q, 4 C), 20.6 (q, 1 C), 20.5 (q, 1 C). HRMS (ESI+): m/z calcd for C34H40F3NNaO18 + [M + Na]+: 830.2090; found: 830.2099.
  • 28 Mikula H, Hametner C, Fröhlich J. Synth. Commun. 2013; 43: 1939
  • 29 General Procedure A: Silver(I)-Activated Königs–Knorr Glycosylation Using Gentiobiosyl Bromide 7 To a solution of the glycosyl acceptor (1 equiv) and gentiobiosyl bromide 7 (2.5 equiv) in CH2Cl2 or MeCN (5 mL/mmol) MS 3 Å (0.1 g/mL) was added, and the reaction mixture was stirred at r.t. under argon for 1 h. After addition of silver(I) salt (1.5 equiv) stirring was continued in the dark for an additional period of 48 h. Filtration through Celite and concentration under reduced pressure afforded the crude product mixture.
  • 30 General Procedure B: Lewis Acid Mediated Glycosylation Using Acetimidate 10 To a solution of the glycosyl acceptor (1 equiv) and gentiobiosyl bromide 7 (1.5–2.5 equiv) in CH2Cl2 or dioxane–toluene (5 mL/mmol) MS 3 Å (0.1 g/mL) was added, and the reaction mixture was stirred at r.t. under argon for 1 h. After cooling to –10 °C, TMSOTf or BF3·OEt2 (0.02–0.1 equiv) was added, and stirring was continued at –10 °C for an additional period of 16 h. The reaction mixture was filtered through Celite, washed with sat. aq NaHCO3, dried over Na2SO4, and concentrated under reduced pressure to afford the crude product mixture.
  • 31 General Procedure C: Phase-Transfer Glycosylation Using Gentiobiosyl Bromide 7 Glycosyl acceptor (1 equiv), 7 (2.8 equiv), and TBAB (1 equiv) were dissolved in CHCl3 (80 mL/mmol). Borate buffer (80 mL/mmol) was added, and the reaction mixture was warmed to 45 °C. The pH was kept between 10.5 and 11.0 by dropwise addition 0.1 M aq NaOH. After 6 h the organic layer was separated, dried over Na2SO4, and concentrated to afford the crude product mixture.
  • 32 General Procedure D: Basic Hydrolysis of Crude Acetyl-Protected Gentiobiosides Crude acetyl-protected gentiobioside (12 or 14) was filtered over silica gel (hexanes–EtOAc = 3:1 to 1:2) to remove most of the carbohydrate impurities. Appropriate fractions were pooled and concentrated. The residue was dissolved in THF–H2O (4:1, 50 mL/mmol), KOH (10 equiv) was added, and the reaction mixture was stirred for 2 h at r.t. After addition of 0.1 N HCl (pH 6.8), the solution was diluted with H2O and immediately extracted with EtOAc. The combined organic layer was dried over Na2SO4 and concentrated. RP-C18 column chromatography (MeCN–H2O gradient elution, used for 13) or preparative RP-C18-HPLC (MeCN–H2O gradient elution, used for 3) yielded the desired gentiobioside.
  • 33 Synthesis of Gentiobioside 13 Starting from ZEN mimic 11 (11.7 mg, 0.06 mmol) and following general procedures C and D, gentiobioside 13 was obtained as a white solid (9.3 mg, 30%). Analytical Data for 13 1H NMR (400 MHz, MeOD): δ = 7.77 (d, J = 8.8 Hz, 1 H), 6.71 (d, J = 1.8 Hz, 1 H), 6.64 (dd, J = 8.8, 1.8 Hz, 1 H), 5.26 (sept, J = 6.2 Hz, 1 H), 4.98 (d, J = 6.9 Hz, 1 H), 4.36 (d, J = 7.5 Hz, 1 H), 4.17 (d, J = 11.3 Hz, 1 H), 3.91–3.83 (m, 1 H), 3.88–3.78 (m, 2 H), 3.81–3.74 (m, 1 H), 3.67 (dd, J = 11.3, 5.4 Hz, 1 H), 3.50–3.44 (m, 2 H), 3.44–3.38 (m, 1 H), 3.36–3.30 (m, 1 H), 3.28–3.20 (m, 2 H), 1.38 (d, J = 6.2 Hz, 6 H). 13C NMR (100 MHz, MeOD): δ = 170.7 (s, 1 C), 164.6 (s, 1 C), 164.4 (s, 1 C), 132.4 (d, 1 C), 109.6 (d, 1 C), 108.4 (s, 1 C), 104.94 (d, 1 C), 104.88 (d, 1 C), 101.32 (d, 1 C), 78.0 (d, 1 C), 77.9 (d, 1 C), 77.8 (d, 1 C), 77.3 (d, 1 C), 75.1 (d, 1 C), 74.7 (d, 1 C), 71.6 (d, 1 C), 71.4 (d, 1 C), 70.2 (d, 1 C), 70.1 (t, 1 C), 62.7 (t, 1 C), 22.1 (q, 2 C). HRMS (ESI): m/z calcd for C22H31O14 [M – H]: 519.1719; found: 519.1707.
  • 34 Synthesis of ZEN-14-β,d-gentiobioside (3) Starting from ZEN (1, 33.4 mg, 0.105 mmol) and following general procedures C and D, ZEN-14-β,d-gentiobioside (3) was obtained as a white solid (29 mg, 43%). Analytical Data for 3 1H NMR (400 MHz, DMSO-d 6): δ = 10.43 (br s, 1 H), 6.65 (d, J = 1.5 Hz, 1 H), 6.53 (d, J = 1.5 Hz, 1 H), 6.40 (d, J = 15.4 Hz, 1 H), 6.01 (dt, J = 15.4, 7.1, 1 H), 5.36 (d, J = 4.3 Hz, 1 H), 5.18 (d, J = 3.2 Hz, 1 H), 5.11–5.04 (m, 1 H), 4.98–4.86 (m, 2 H), 4.90 (d, J = 7.8 Hz, 1 H), 4.53 (br s, 1 H), 4.19 (d, J = 7.8 Hz, 1 H), 3.98 (d, J = 10.2 Hz, 1 H), 3.66 (d, J = 12.1 Hz, 1 H), 3.63–3.55 (m, 2 H), 3.47–3.41 (m, 1 H), 3.30–3.18 (m, 3 H), 3.16–3.09 (m, 1 H), 3.08–3.03 (m, 2 H), 2.98 (t, J = 8.1 Hz, 1 H), 2.39–2.32 (m, 1 H), 2.32–2.26 (m, 2 H), 2.25–2.16 (m, 1 H), 2.07–1.95 (m, 1 H), 1.83–1.71 (m, 1 H), 1.70–1.59 (m, 3 H), 1.58–1.45 (m, 2 H), 1.27 (d, J = 6.1 Hz, 6 H). 13C NMR (100 MHz, DMSO-d 6): δ = 211.2 (s, 1 C), 168.7 (s, 1 C), 160.0 (s, 1 C), 158.5 (s, 1 C), 138.4 (s, 1 C), 133.3 (d, 1 C), 129.8 (d, 1 C), 112.8 (s, 1 C), 105.2 (d, 1 C), 103.9 (d, 1 C), 103.1 (d, 1 C), 100.6 (d, 1 C), 77.3 (d, 1 C), 77.1 (d, 1 C), 76.8 (d, 1 C), 74.0 (d, 1 C), 73.6 (d, 1 C), 71.9 (d, 1 C), 70.4 (d, 1 C), 69.9 (d, 1 C), 68.9 (t, 1 C), 61.4 (t, 1 C), 43.5 (t, 1 C), 37.1 (t, 1 C), 34.8 (t, 1 C), 31.4 (t, 1 C), 21.4 (t, 2 C), 20.3 (q, 2 C). HRMS (ESI): m/z calcd for C30H41O15 [M – H]: 641.2451; found: 641.2455.