反应详情

温度

37 °C

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).

1. customsynthesis of 1
2. filtrationAfter the resin was filtered off
3. washwashed with water
4. customa solution of 2 (18.60 mL, 10.0 mmol, synthesized by Wong, C.-H. J. Org. Chem. 1994, 59, 7182)
5. additionwas added
6. additionwas added
7. customthe solution was degassed with argon
8. additionwas added
9. temperatureThe mixture was then cooled to room temperature
10. additionwere added
11. additionMethanol (2 vol) was then added
12. filtrationthe precipitate was filtered off through Celite
13. washwashed with MeOH (4×25 mL)
14. customMeOH was removed under reduced pressure (bath temp. <25° C.) and water (100 mL)
15. additionwas added on the aqueous residue
16. extractionthe mixture was continuously extracted with AcOEt for 48 h
17. extractionThe organic extract
18. customthe aqueous solution evaporated under reduced pressure (bath temp. <25° C.)
19. additionThe residue was treated with methanol (50 mL)
20. customthe white solid formed
21. filtrationwas filtered off
22. washwashed with more methanol (2×15 mL)
23. additionCharcoal was added to the filtrate
24. temperaturethe mixture heated at 30° C. for 15 min
25. filtrationAfter filtration
26. customto remove charcoal, methanol
27. customwas removed
28. additiontoluene was added time to time
29. customto remove traces of water (bath temp. <25° C.)
30. customAfter removing the solvents
31. dissolutionthe residue was dissolved in hot absolute ethanol (12.5 mL)
32. waitstored at 4° C. for 2 days