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Preparation of 5a: β-d-Glucose penta-O-acetate (0.36 g, 0.92 mmol) and boron trifluoride diethyl etherate (0.13 ml, 0.92 mmol) were added to a solution of p-cresol (0.2 g, 1.84 mmol) in CH2Cl2 (5 mL) containing molecular sieves (4 Å, activated). The resulting reaction mixture was protected from moisture and stirred at 25-30 °C overnight (16 h). The reaction mixture was diluted with CH2Cl2 (40 mL) and washed with aq KOH (2 M, 4 × 25 mL), water (2 × 25 mL) and brine (25 mL). The organic extracts were dried (MgSO4) and concentrated under reduced pressure to afford a crude off-white solid. The crude product was recrystallised from anhyd EtOH to afford 5a (214 mg, 53%) as colourless crystals; Rf 0.70 (2:1 EtOAc-hexane), mp 110-111 °C.
1H NMR (400 MHz, CDCl3): δ = 7.11 (d, J = 8.6 Hz, 2 H), 6.90 (d, J = 8.6 Hz, 2 H), 5.31-5.15 (envelope, 3 H), 5.03 (d, J = 7.3 Hz, 1 H), 4.27 (dd, J = 11.9, 5.0 Hz, 1 H), 4.18 (dd, J = 11.9, 2.3 Hz, 1 H), 3.90-3.79 (m, 1 H), 2.31 (s, 3 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.06 (s, 3 H), 2.04 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.4, 170.1, 169.2, 169.1, 154.6, 132.7, 129.8, 116.9, 99.4, 72.4, 71.9, 71.1, 68.2, 61.9, 20.6, 20.5.
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Preparation of 6a: Compound 5a (0.25 g, 0.57 mmol) was dissolved in MeOH (10 mL) and aq Na2CO3 (2 M, 3.5 mL) was added. The reaction mixture was stirred at ambient temperature for 5 h with monitoring by TLC. The mixture was neutralised with HCl (1 M) and the solvent removed under reduced pressure. The compound was then purified by reverse phase chromatography on a Waters® C18 Sep-Pak column by eluting with water and then with 50% aq MeOH. Appropriate fractions were pooled and the solvent removed under reduced pressure to afford 6a (88 mg, 57%) as a white solid. 1H NMR (400 MHz, D2O): δ = 7.44 (d, J = 8.6 Hz, 2 H), 7.35 (d, J = 8.6 Hz, 2 H), 4.25 (d, J = 9.8 Hz, 1 H), 4.08 (d, J = 3.9 Hz, 1 H), 3.86-3.80 (envelope, 5 H), 2.63 (s, 3 H), 13C NMR (100 MHz, D2O): δ = 155.8, 131.7, 129.7, 116.6, 101.4, 76.9, 73.8, 70.3, 61.4, 19.7. HRMS-FAB+: m/z [M] calcd for C13H18O6: 270.1103; found, 270.1090.
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Preparation of 7a: Glucoside 6a (200 mg, 0.74 mmol) was dissolved in distilled water (10 mL) and TEMPO (0.005 equiv) and NaBr (0.15 equiv) were added. The solution was cooled to 0 °C and a cold solution of 12-15% hypochlorite in water (previously brought to pH = 10 by addition of 4 M HCl) was added. The pH was controlled at ca 10-10.5 by dropwise addition of KOH (0.5 M) with a syringe. The reaction was complete within 30 min (TLC) during which time the pH was generally stable. The reaction was quenched by addition of EtOH (5 mL) and the mixture neutralised with 1 M HCl. The organic solvent was removed under reduced pressure and the remaining solution was freeze-dried. The crude product was purified using either XAD-2 column or Waters® Sep-Pak column chromatography by eluting with water, 50% aq MeOH and MeOH. Appropriate fractions were pooled and the solvent removed under reduced pressure and the crude product freeze-dried to afford pure 7a (176 mg, 74%) as a white solid. 1H NMR (400 MHz, D2O): δ = 7.14 (d, J = 8.7 Hz, 2 H), 6.98 (d, J = 8.7 Hz, 2 H), 4.96 (d, J = 9.2 Hz, 1 H), 3.77 (d, J = 4.0 Hz, 1 H), 3.57-3.53 (envelope, 3 H), 2.13 (s, 3 H). 13C NMR (100 MHz, D2O):
δ = 175.9, 154.9, 133.7, 130.7, 117.1, 100.9, 76.5, 73.2, 72.2, 20.1. HRMS-FAB+: m/z [M + H] calcd for C13H16O7K, 323.0533; found, 323.0521. HRMS-FAB+: m/z [M + K] calcd for C13H15O7K2: 361.0092; found, 361.0059. MS (FAB+): m/z (%) = 361 (10) [M + K], 323 (15) [M + H], 315 (10), 223(40), 131 (100), 39 (27) [K].
