Studies On The Reduction Of Aldehydes And Ketones And The Inhibitors Of Rho Kinase Design, Synthesis And Activity Test

The reduction of ketones and aldehydes to alkanes is an important reaction for chemical industry. The Clemmensen reaction (acidic) andWolff-Kishner-Huangminlon reaction (basic) are the traditional procedures to complete this transformation, but these two methods have a non-friendly impact on the environment. To obtain an effective and non-pollution process, the reduction of carbonyl compounds was researched systematically in the first part of this paper.1, The reduction of benzaldehyde in presence of aniline over Ni30/γ-Al₂O₃ was investigated, and the toluene was obtained with a high yield (96.5%). The whole process consists of nucleophilic addition of aniline to benzaldehyde, elimination of water to the Schiff base, which is hydrogenated to N-benzylaniline, and hydrogenolysis of N-benzylaniline affords toluene and aniline. Aniline acted as a catalyst during the whole process. Finally, this kind of reduction method was employed for the reduction of 4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde, and both yields of the corresponding alkanes were more than 90%.2, Firstly, hypnone was chosen as a model to research the catalytic hydrogenation of aromatic ketones to ethylbenzene, Ni30Cu5/γ-Al₂O₃ and Cu₃0Cr₅/γ-Al₂O₃ were selected as the catalysts, and the correspounding yields of ethylbenzene were 94.8% and 99.1%. Then, cyclohexanone was chosen as a substrate to study the reduction of aliphatic ketones. Ni/HZSM-5(38v1)was chosen as catalyst, and the yield of cyclohexane is 76.6%. The process proceeds through the hydrogenation of ketones to alcohol, dehydration of the alcohol to olefin and subsequent hydrogenation of the double bond to alkanes. Finally, the reduction of aromatic aldehydes was also researched with benzaldehyde as a substrate. Ni30/γ-Al₂O₃ was select as the catalyst, and the yield of toluene was 88.9%.Rho kinase was a new target spot of heart head blood-vessel, and Rho kinase inhibitors were a kind of new effictive drugs for heart head blood-vessel. In the second part of this paper, the Rho kinase inhibitor was designed, synthesized and tested.1, The synthetic rute of hydroxyfasudil was estiblished. It was obtained from Fasudil through the protection of the aminogroup, oxidation of Boc-Fasudil, rearrangement of Boc-Fasudil N-oxide and finally deprotection in a total yield of 46.8%. 2, A series of Rho inhibitors were designed and synthezed, and their inhibiting activity of Rho kinase, MTT, and LDH were tested. It was found that compound 8 and compound 9 exhibit excellent activity, better cell activity and less cell apoptosis than Fasudil. compound 8 and compound 9 have the protential to be new drugs.