求：辅酶Q10合成工艺或专家？ 2004美国专利做辅酶q10的方法！ [0023] step 1: solanesol. [0024] one kg of tobacco dust is shaken with 41 of hexane for 1.5 hours. the solid is separated by filtration and extracted with a total of 2.4 l of hexane. the combined extracts are evaporated. to the resulting residue are added 140 ml of 2 n koh in ethanol and 2 g of pyrogallol. the obtained mixture is heated for 1 hour (reflux) under n.sub.2. it is then rapidly cooled, 400 mg of a 9:1 mixture of ethanol and water is added and this mixture extracted with hexane (4.times.400 ml). the extract is dried with sodium sulfate and chromatographed on a column of 300 g of alumina. after elution with a 9:1 mixture of hexane/ether and evaporation, 5 g of solanesol are obtained. [0025] step 2: solanesylacetone. [0026] to a solution of 10 g of solanesol obtained in step 1 in a mixture of 9.5 ml of anhydrous hexane and 13.5 ml anhydrous ether, at 0-5 degree c., there are added 1.3 ml of pyridine. thereafter over a period of 35 minutes, 1.8 ml of phosphorous tribromide in 13 ml of hexane are added. the resulting mixture is stirred, at 0-5 degrees c. for 3 hours and then added to ice water, and then stirred for an additional 10 minutes. the organic phase is separated off, and the aqueous layer extracted with ether, washed with 5% sodium bicarbonate water, and then dried with magnesium sulfate. after evaporation, 11 g of solanesol bromide are obtained. 2.5 g of ethyl acetoacetate are added to the solanesol bromide followed by the addition of a solution of 0.4 g of sodium in 18 ml absolute alcohol, over a period of 20 minutes while maintaining a temperature of 10 degrees c. the resulting reaction mass is kept at 20 degrees c. for 12 hours. it is then heated to 80 degrees c., and 2.5 ml of 10% naoh are added over 1 hour. the mixture is then stirred at 80 degrees c. for 4 hours, poured into ice water and extracted with ether, the ether solution is washed with water and dried with magnesium sulfate and evaporated. the yield is 8 g of solanesylacetone obtained as a solid. [0027] the chemical reactions can be seen in the following formulas: 2 [0028] step 3 :--isodecaprenol . [0029] to 1.4 g of magnesium in 18 ml anhydrous thf (under n.sub.2) a small crystal of iodine, a drop of methyl iodide and 0.1 ml of vinyl bromide are added. after the onset of the exothermic reaction, 4 ml vinyl bromide in 9 ml thf are gradually added while the temperature is maintained at about 50 degrees c. the mixture is stirred at 50-60 degrees c. for 1 hour to complete the formation of vinyl-magnesium bromide. the mixture is then cooled to 0-5 degrees c. and 8 g of solanesylacetone in 32 ml thf are added over a period of 10 minutes. the mixture is left at 20 degrees c. for 3 hours after which it is cooled to 0-5 degrees c. a solution of 4.2 g ammonium chloride in 10 ml of water is added, and mixture is stirred for 10 minutes and is then extracted with ether, washed with water and dried with magnesium sulfate. after evaporation, 9 g of isodecaprenol were obtained as a colorless, waxy substance. [0030] step 4:-2, 3, 6-tribromo-4-methylphenol-9108 g (1 mol) p-cresol is dissolved in 120 l of chloroform containing 4 g iron powder and 500 g bromine are then introduced drop wise over a period of 5 hours at room temperature. the resulting solution is stirred for 48 hours and then filtered, washed with dilute sodium sulfite and dried with magnesium sulfate. the solvent is evaporated and the residue recrystallized from hexane. a yield of 265 g is obtained. 3 [0031] step 5:--2,3,4,5-tetramethoxytoluene. [0032] sodium (23 g) is dissolved in 400 ml of methanol. to this 9.3 g dme and 50 ml dimethyl carbonate are added to the resulting solution. most of the methanol (300 ml) is then removed by distillation; 915 g of copper cyanide are added and a solution of 34.4 g 2,3,6-tribromo4-methylphenol in 100 ml dme prepared and is added drop wise over a period of 3 hours, with stirring, while maintaining the temperature at 80 degrees c. the mixture is stirred an additional 5 hours while continuing to maintain the 80 degrees c. temperature. to this mixture, 800 ml of water is added, the mixture is cooled to 50 degrees c. 100 ml dimethyl sulfate is then added in drop wise fashion. the mixture is then stirred at room temperature for 2 hours and concentrated. 250 ml aqueous ammonium hydroxide are then added. the mixture is extracted with methylchloride and the organic extract washed with dilute hcl and water and dried over magnesium sulfate. the solvent is evaporated off leaving 20 g of pure product; bp 100 c. (0.1 mm). 4 [0033] step 6:--2,3 dimethoxy-5-methylhydroquinone. [0034] 33.4 g of pyridine-2,6 dicarboxylate was added to a cold, 0 degree c., solution of 2,3,4,5 tetramethoxytoluene (17 g) in 400 ml of acetonitrile/water (7:3). a cold solution, 0 degree c., of ceric ammonium nitrate, 110 g in 400 ml of 1:1 acetonitrile/water is slowly added over 20 minutes, and the mixture stirred for 20 minutes at 0 degree c. and for 10 minutes at room temperature. the reaction mixture is poured into 400 ml of water and extracted with methyl chloride. the organic layer is dried over magnesium sulfate, evaporated and chromatographed on silica gel, (hexane/ethylacetate 20:1, yielding 14 g of red crystals, mp 59 degrees c. 5 [0035] step 7:--ubiquinone coenzyme q10. [0036] equimolar portions of portions of the products obtained in step 3 ( isodecaprenol )and 6 (2,3 dimethoxy-5-methyl hydroquinone) are stirred at 43 degrees c. for 10 minutes in hexane. a 2.5% sodiumbisulfite solution is added, and the hexane layer separated, dried over magnesium sulfate, concentrated and chromatographed on silica gel (hexane/ether 10:1) to give ubiquinone as a yellow solid. 6 [0037] the administration of optically pure coenzyme q10 can be oral, parenteral or topically, in the latter case for the treatment of diseases of skin and mucous membranes. oral administration is favored over parenteral administration due to the very low solubility of coenzyme q10 in excipients compatible with is parenteral administration. oral administration has proved particularly useful in the treatment of diseases affecting metabolically very active organs, whereas coenzyme q 10 if administered orally proves to be substantially ineffective at the cutaneous level. accordingly the concentration of coenzyme q 10 has to be increased for topical administration directly to impaired or damaged tissue. [0038] the oral form of administration can be as pills, tablets, capsules or liquid preparations in each case formulated in the conventional manner with suitable carriers and formulation aids. the formulations are prepared to deliver 5-100 mg per dosage unit and in some instances up to 200 mg per dosage units of the optically pure coenzyme q 10. [0039] the compositions for topical administration can be prepared by dissolving or suspending coenzyme q 10 in vegetable oils such as corn oil, canola oil, or soy bean oil, lecithin, glycerol, glycerylfurole, tween 80 or other derivatives, suspending agents or diluents. after the addition of suitable carriers and formulation aids to such solutions or suspensions, the compositions can be forwarded as pastes, creams, ointments, gels, lotions, unguents. [0040] the compositions for topical application contain the optically pure coenzyme 10 as the active principal in amounts from 0.1 to 10%, preferably from 0.25 to 1%. the topical compositions can also be used for cosmethological purposes. in such a case, the content of coenzyme q 10 can be lower than the limits aforementioned being preferably from 0.0001 to 0.1%. 呵呵，转贴的！ 查看更多
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