Sodium Hydroxide → L-(-)-Fucose

참여 물질

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반응 단계

Scaled up sequential synthesis of 1. Compound 6 (6.0 g, 50 mmol) was hydrolyzed in water (50 mL) with Dowex 50W-X8 resin (H+ form, 200-400 mesh, 6.0 g, pH 2.8) for 4 h at 60° C. After the resin was filtered off and washed with water, a solution of 2 (18.60 mL, 10.0 mmol, synthesized by Wong, C.-H. J. Org. Chem. 1994, 59, 7182) was added, the mixture adjusted to pH 6.8 with 6N NaOH (1.8 mL) and L-fuculose aldolase (24 mL, 305 units) was added. The mixture was readjusted to pH 6.8 with 6N NaOH (0.2 mL) and the solution was degassed with argon and protected from light. After 3 h at room temperature (DHAP analysis indicates 95% conversion) the mixture was adjusted to pH 4.7 with 6N HCl (1.8 mL), acid phosphatase (1.33 mL, 400 units) was added and the mixture heated at 37° C. for 18 h. The mixture was then cooled to room temperature and adjusted to pH 7.5 with 6N NaOH (2.6 mL). MnCl2 (1 ml, 0.11 M) and L-fucose isomerase (4 mL, 3280 units) were added. The mixture was stirred at room temperature for 9 h and adjusted to pH 7.0 with 6N HCl. Methanol (2 vol) was then added and the precipitate was filtered off through Celite and washed with MeOH (4×25 mL). MeOH was removed under reduced pressure (bath temp. <25° C.) and water (100 mL) was added on the aqueous residue and the mixture was continuously extracted with AcOEt for 48 h. The organic extract was discarded and the aqueous solution evaporated under reduced pressure (bath temp. <25° C.). The residue was treated with methanol (50 mL) and the white solid formed was filtered off, washed with more methanol (2×15 mL) and discarded. Charcoal was added to the filtrate and the mixture heated at 30° C. for 15 min. After filtration to remove charcoal, methanol was removed and toluene was added time to time to remove traces of water (bath temp. <25° C.). After removing the solvents, the residue was dissolved in hot absolute ethanol (12.5 mL), seeded with 1 and stored at 4° C. for 2 days. Compound 1 (543 mg, 3.3 mmol, 33.1%) was obtained as a white solid whose physical and spectroscopic data were in accordance with those from an authentic sample: m. p. 139-140° C.; [α]D=−76.6° (c=0.9, water).

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