The Synthesis Of Coenzyme Q Derivatives

Coenzyme Q is a kind of low molecular compound which is widely existing in the mitochondrion of organism, including human body. It has a vital importance in the electron transformation, and regulation of metabolism. Many Coenzyme Q derivatives were become the drug for us.In the paper, we modified the structure of Coenzyme Q in the 6th position. As a result, kinds of Coenzyme Q derivatives were got. The paper included two parts, those were the synthesis of the nucleus structure, and the synthesis of the Coenzyme Q derivatives.1 The synthesis of the nucleus structuresIn the paper, three kinds of the nucleus structures were prepared. These three kinds of nucleus structures were 3,4,5-trimethoxyltoluene,2,3,4,5-trimethoxyltoluene and 2,3,4-trimethoxyl-6-methylphenol.3,4,5-trimethoxyltoluene was synthesized from 3,4,5-trimethoxybenzaldehyde by the Wollf-Kishner-Huangminglong Reaction. After our improvment, the yield of the reaction was 97.8%.The compound 2,3,4,5-tetramethoxytoluene was synthesized from 3,4,5-trimethoxyltoluene by selectively bromination with NaBr and 30% H2O2, and methoxylation with high concentration of sodium methoxide in the presence of CuCl or CuBr, which amounted to two steps with the overall yield of 84.1%.The compound 2,3,4-trimethoxyl-6-methylphenol were synthesized from 3,4,5-trimethoxyltoluene by Vilsmeier Reaction, Dakin Reaction, with the overall yield of 35%.2 The preparation of Coenzyme Q derivativesThe compound, with high activity,2,3,4,5-tetramethoxyl-6-methylbenzylchloride was synthesized from 2,3,4,5-tetramethoxytoluene by Blanc Reaction.In the paper, two kinds of modification structure were prepared, those were the compounds which had ether groups in the 6th position, and the compounds which had piperazinyl groups in the 6th position.After our improvement, the yield of the compounds with piperazinyl groups was about 40-60%, and the procedure of the reaction was much easier, as well.The compounds with ether groups which were prepared in the above, could be changed into the corresponding Ubiquinones in the appearance of Ammonium ceric nitrate (CAN).While the compound with piperazinyl group, can not be changed into the Ubiquinone in a satisfied yield and purity. So the Ubiquinones with piperazinyl groups were prepared with 2,3,4,5-tetramethoxyl-6-methylphenylchloride as the raw material, followed by the oxidation of CAN, and then the reaction with N-phenylpiperazine or benzoylpiperazine.In the paper, some research about the preparation of N-phenylpiperazine and benzoylpiperazine was carried out. And our method was highly in yield, and easily in the procedure.In the paper,38 compounds were prepared, including 16 newly synthesized ones, and 9 Ubiquinone compounds. Most of Ubiquinones were verified by 1H NMR.