Hydrochloric Acid → 6-Methoxy-L-fucose

Temperatur

50 °C

A method for synthesizing 6-methyl-L-fucose is illustrated in Scheme 2. Compound 7e, the starting material, was synthesized according to the method of Wong et. al. (J. Am. Chem. Soc., 1986, 108, 7812, (1.21 g; 10.1 mmol). Compound 7e was dissolved in water (3 mL) and Dowex 50W-X8 (H+ form, 200-400 mesh) was added until pH 2.8. The mixture was heated at 50° C. for 8 h, then the resin was filtered off and washed with water (2×0.5 mL). A solution of 2, as synthesized by Wong, C.-H. et. al. J. Org. Chem. 1994, 59, 7182, (4.62 mL, 1.68 mmol) was added and the mixture was adjusted to pH 6.8 with 6N NaOH (0.4 mL). L-fuculose aldolase (5.2 mL, 50 units) previously prepared by Wong, C.-H. et. al. Bioorg. Med. Chem. 1995, 3, 945, was added, the mixture was stirred gently at room temperature for 17 h (DHAP analysis indicates 95% conversion) and the pH was adjusted to 4.7 with 6N HCl (0.4 mL). Acid phosphatase (0.45 mL, 225 units) was added and the mixture heated at 37° C. for 19 h. The mixture was cooled to room temperature and the pH was adjusted to 7.5 with 6N NaOH (0.6 mL). MnCl2 (30 μl, 0.7 M) and L-fucose isomerase (3 mL, 2460 units) were added. The mixture was stirred at room temperature for 24 h and adjusted to pH 7.0 with 2N HCl. Methanol (2 vol) was then added and the precipitate was filtered off through Celite. The solvent was removed under reduced pressure and the residue chromatographed on silica gel with CHCl3/methanol (3:1). The fractions containing L-fucose 8e were pooled, then concentrated and the residue chromatographed on Dowex 50W-X8 (Barium form, 200-400 mesh) with water/ethanol (1:1) to yield 8e as a white-yellowish solid (63 mg, 0.3 mmol, 25%). [α]D=−14.4 (c=1, MeOH, 4 h), [Lit, [α]25eq=−80.6 (c=1, pyridine, eq)]. 1H-NMR (400 MHz, D2O) δ: 5.10 (H1α, d, JH1α,H2α=3.6 Hz), 4.42 (H4β, d, JH1β,H2β==8 Hz), 4.08 (H5α, t, JCH2,H5α=6 Hz), 3.81 (H4α, d, JH4α,H3α=3 Hz), 3.75 (H4β, d, JH4β,H3β=3.5 Hz), 3.6-3.7 (H2α, H3α, H5β, overlapped signals), 3.58 (CH3O—, α and β), 3.47-3.52 (H3β and CH2 α and β, overlapped signals), 3.32 (H2β, dd, JH1β,H2β=8 Hz, JH2β,H3β=10 Hz) 13C-NMR (100 MHz, D2O) δ (ppm): 96.31 (C1β), 92.19 (C1α), 73.17, 72.61, 71.82, 71.61, 69.46, 68.93, 68.44, 68.19, 59.29 (CH3), 58.35 (C6β), 58.20 (C6α). HRMS Calcd for C7H14O6+Na+ 217.0688, observed 217.0647.

1. addition(H+ form, 200-400 mesh) was added until pH 2.8
2. filtrationthe resin was filtered off
3. washwashed with water (2×0.5 mL)
4. customA solution of 2, as synthesized by Wong, C
5. addition1994, 59, 7182, (4.62 mL, 1.68 mmol) was added
6. addition1995, 3, 945, was added
7. additionAcid phosphatase (0.45 mL, 225 units) was added
8. temperaturethe mixture heated at 37° C. for 19 h
9. temperatureThe mixture was cooled to room temperature
10. additionwere added
11. filtrationthe precipitate was filtered off through Celite
12. customThe solvent was removed under reduced pressure
13. customthe residue chromatographed on silica gel with CHCl3/methanol (3:1)
14. additionThe fractions containing L-fucose 8e
15. concentrationconcentrated
16. customthe residue chromatographed on Dowex 50W-X8 (Barium form, 200-400 mesh) with water/ethanol (1:1)

ORD-Eintrag

ord-3022ee2fa058464781d5dd0b3b339f36

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06713287B1