39%; 37% |
With pyridine; sodium hydroxide; In methanol; for 1.5h; |
d-(+)-Glucurono-6,3-lactone (20.0 g, 113.55 mmol) was dissolvedin methanol (150 mL) containing NaOH (0.03 g, 0.75 mmol)and the solution was stirred until the lactone had completely dissolved.The solvent was removed under vacuum. The resulting syrupwas dissolved in acetic anhydride (65 mL, 688.90 mmol) and pyridine(10 mL) was added dropwise over 30 minutes. The solution wasstirred for 1 hour and the solvent volume was reduced to 40 mLunder reduced pressure. The solution was refrigerated for 12 hoursafter which crystalline material precipitated. This was isolated andrecrystallised from ethanol to yield methyl tetra-O-acetyl-beta-dglucopyranuronate(1) (16.65 g, 39%) as a white crystalline solid.M.p. = 177-179 C (ethanol) (Lit.1 = 177-178 C), [alpha]D20 +9.0 (c 1.0CHCl3), numax/cm-1 (KBr disc) 2956 (C-H), 1749 (C=O), 1379 (CH),1216 (O-C=O), 1019 (C-O-C). deltaEta(CDCl3) (beta anomer). 2.04 (3H, s,OAc), 2.05 (6H, s, 2 × OAc), 2.12 (3H, s, OAc), 3.75 (3H, s, CO2Me),4.17 (1H, d, 3J = 9.2 Hz, H-5), 5.15 (1H, dd, 3J = 9.2 & 7.6 Hz, H-2), 5.24(1H, t, 3J = 9.2 Hz, H-4), 5.31 (1H, t, 3J = 9.2 Hz, H-3), 5.76 (1H, d,3J = 7.6 Hz, H-1). deltaC (CDCl3) (beta anomer) 20.40 (CH3CO), 20.47 (CH3CO),20.49 (CH3CO), 20.70 (CH3CO), 52.94 (CH3O), 68.89 (CH), 70.14 (CH),71.78 (CH), 72.94 (CH), 91.33 (CH), 166.78 (C=O), 168.76 (C=O),169.11 (C = O), 169.35 (C=O), 169.83 (C=O). HRMS (ESI): calcd. forC15H24NO11 [M + NH4]+ 394.1349; found 394.1337. The mother liquorwas evaporated and the residue was subjected to flash chromatography(50:50 ethyl acetate: hexane) to yield an oil. Trituration withethanol gave methyl tetra-O-acetyl-alpha-d-glucopryranuronate (3)(15.8 g, 37%) as a white crystalline solid. M.p. = 106-108 C, [alpha]D20+61.0 (c 2.0 CHCl3), deltaEta (CDCl3) (alpha anomer) 1.98 (3H, s, OAc), 2.05 (6H,s, 2 × OAc), 2.12 (3H, s, OAc), 3.76 (3H, s, CO2Me), 4.34 (1H, d,3J = 10.0 Hz, H-5), 5.21 (1H, dd, 3J = 8.0, 3.6 Hz H-2), 5.24 to 5. 33 (2H,m, H-3 & H-4), 6.34 (1H, d, 3J = 3.6 Hz, H-1). deltaC (CDCl3) (alpha anomer)20.50 (CH3CO), 20.64 (CH3CO), 20.71 (CH3CO), 20.79 (CH3CO), 52.95(CH3O), 71.45 (CH), 72.70 (CH), 73.07 (CH), 73.15 (CH), 91.34 (CH),167.17 (C=O), 169.02 (C=O), 169.57 (C=O), 170.24 (C=O), 170.37(C=O). HRMS (ESI): calcd. for C15H24NO11 [M + NH4]+ 394.1349; found394.1328. |
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To commercially available <strong>[32449-92-6]D-glucurono-6,3-lactone</strong> compound (6) (48.6276 mmol), was added anhydrous methanol (500 mL) and Na metal (200 mg) at 0C. Themixture was stirred under N2 for 5 h. The solution was treated with Amberlite IR- 120(Ir) resin until pH 3. After filtration the solvent was removed in vacuo to give a yellow gum. The residue was partially dissolved in Ac20 (100 mL), and a solution of HC1O4 (0.1 mL) in Ac20 (1 mL) was added dropwise to the reaction mixture at such a rate that the solution did not exceed 40C. The reaction mixture was then stirred overnight at rtunder N2. The product was then dissolved in ethyl acetate, washed with 1 N HC1, H20, and brine, the organic phase was dried over Na2SO4.The solvent was removed in vacuo to afford per-O-acetate intermediate compound (5) (96.5 g, 93%) as a white gum with an ct/f3 ratio of 75:25. The spectroscopic data was consistent with previously reported spectroscopic data (1)1H NMR (400 MHz, CDC13): x-anomer 6.42 (d, 1 H, J= 3.9 Hz, 1H); 5.54 (dd,1 H, Ji = 10.0, J2 = 9.7 Hz, 1H); 5.24 (dd, 1 H, Ji = 10.2, J2 = 9.7 Hz,1 H); 5.14 (dd, 1 H, Ji = 10.0, J2 = 3.9 Hz, 1H); 4.43 (d, 1 H, J = 10.2 Hz, 1H); 3.77 (s, 3 H, CO2Me); 2.21, 2.06, 2.03 (3 s, 12 H, 4 OAc).1H N1VIR (400 1VIHz, CDC13): f3-anomer 5.75 (d, 1 H, J = 7.8 Hz, 1 H); 5.32 -5.09 (m, 3 H); 4.16 (d, 1 H, J = 9.3 Hz, H-5); 3.73 (s, 3 H, CO2Me); 2.10, 2.02, 2.01 (3 s,12 H, 4 OAc). |