半化学法合成辅酶Q_(10)

Simi-Chemical Synthesis of Coenzyme Q_(10)

以3,4,5-三甲氧基甲苯(Ⅰ)为原料,经过Vilsmeier-Haack反应合成6-甲基-2,3,4-三甲氧基苯甲醛(Ⅱ)(收率94.1%).Ⅱ经过Dakin反应得到2,3,4-三甲氧基-6-甲基苯酚(Ⅲ)(收率96.2%).用溴化苄对(Ⅲ)进行酚羟基保护得到2,3,4-三甲氧基-6-甲基苯苄基醚(Ⅳ)(收率95.0%).Ⅳ与1-苯磺酰基-2-甲基-4-羟基-2-丁烯(Ⅴ)在Lewis酸溴化锌的催化作用下发生傅-克烷基化反应得到3-(4-苯磺酰基-3-甲基-2-丁烯)-基-4,5,6-三甲氧基-2-甲基苯苄基醚(Ⅵ)(收率68.9%).Ⅵ与茄呢基溴(Ⅶ)偶联得到接砜产物(Ⅷ)(收率51.0%).Ⅷ经乙醇钠脱砜、硝酸铈铵氧化得辅酶Q10(Ⅸ)(收率45%).产物经熔点测定、1H NMR和FTIR分析鉴定和确证结构.

Coenzyme Q10 （Ⅸ ） was synthesized from 3,4,5-trimethoxytoluene （Ⅰ ）. 6-Methyl-2,3,4-trimethoxy- phenol （Ⅲ） was obtained through Vilsmeier-Haack reaction and Dakin reaction with 94.1% and 96.2 % yield respectively. Phenolic hydroxyl protection of Ⅲ with benzyl bromide gave 6-methyl-2,3,4-trimethoxy phenyl benzyl ether （Ⅳ） in 95.0% yield. Friedel-Crafts alkylation reaction between Ⅳ and 1-phenylsulfonyl-2- methyl-4-hydroxy-2- butene（Ⅴ ） with Lewis acid as catalyst gave 68. 9% yield. The final product coenzyme Q10 （Ⅸ） was synthesized by coupling reaction between 3-（ 3-methyl-4-paratoluenesufonyl - 2-butenyl）-4,5,6-trimethoxy -2-methylphenyl benzyl ether（ Ⅵ） and solanesyl bromide （Ⅶ） followed by reduction and oxidation of the corresponding intermediates, gave 45.0% yield. The structure of the aim product is confirmed by FTIR and ^1H NMR.