反应详情

The synthetic route to Mitoquinone-C5 is shown in FIG. 2B. Dihydropyran (46.83 g, 0.55 mol) was added to 2,3-dimethoxy-5-methyl-1,4-benzohydroquinone (CoQ0) (50 g, 0.275 mol) dissolved in acetic acid (500 mL) and stirred at room temperature for 10 minutes. To this solution was added BF3.Et2O (38.57 g, 0.271 mol). The resulting solution was stirred for 18 hours at room temperature. After this time the crude reaction mixture was poured into iced water (500 mL) and extracted with chloroform (1000 mL). The organic extract was washed with brine (500 mL) and dried (MgSO4). The solvent was removed in vacuo to give the crude 2,3-dimethoxy-5-methyl-6-(tetrahydro-pyran-2-yl)-4-(tetrahydro-pyran-2-yloxy)-phenol (7) as a red oil (115 g) which was used without further purification. A solution of crude 7 (110 g) in a mixture of acetic acid/perchloric acid (97.5:2.5, 500 mL) was hydrogenated over 5% palladium/charcoal (5.42 g) at atmospheric pressure and room temperature until hydrogen uptake ceased (three days). The reaction mixture was then filtered through a pad of Celite, and the solid residue washed with ethanol (500 mL). The combined filtrate was divided into three equal portions and each portion added to distilled water (1000 mL) and extracted with CH2Cl2 (2×200 mL). The combined organic extracts were washed with brine (500 mL), saturated sodium bicarbonate (500 mL), brine (300 mL) and then dried (NgSO4). The mixture was then filtered and solvents were removed in vacuo to give crude 4-acetoxy-3-(5-acetoxy-pentyl)-5,6-dimethoxy-2-methyl-phenyl acetate (8) as a red oil (110 g) which was used in the subsequent step without further purification. 1H NMR δ4.0-4.15 (2H, m, —CH2—O), 3.86 (6H, s, 2×OMe), 2.58 (2H, t, J=7.0 Hz, —CH2—Ar), 2.12 (3H, s, Ar-Me), 2.06 (6H, s, 2×CH3—C═O), 2.02 (3H, s, CH3—C═O), 1.35-1.70 (6H, m, —CH2CH2CH2—) ppm.

1. stirringThe resulting solution was stirred for 18 hours at room temperature
2. customAfter this time the crude reaction mixture
3. extractionextracted with chloroform (1000 mL)
4. extractionThe organic extract
5. washwas washed with brine (500 mL)
6. dry with materialdried (MgSO4)
7. customThe solvent was removed in vacuo