The Synthesis Of Benidipine Hydrochloride And ?-Carboline Derivatives

The dissertation contains two chapters.In chapter one the synthetic process of benidipine hydrochloride,a calcium channel blocker,was investigated.At first the types of antihypertensive drugs and the mechanism of benidipine hydrochloride were introduced,then several reported synthetic routes were reviewed.Through the comparison of the different routes,a suitable synthetic route was selected and improved based on the forth route.The product was obtained via Hantzsch reaction,hydrolysis,esterification and salt formation reaction suing nitrobenzaldehyde and methyl acetoacetate as raw material.During the study the effect of the reaction temperature,reaction time,the types of reagents and solvents and the ratio of reagents were investigated.We also focused on the influense of the different work-up methods for some key intermediates and final product on the yield and purity.After optimization the final product was obtained in 17.9%yield with 99.9%HPLC purity.At last the impurities in benidipine hydrochloride were identified and synthesized.In second chapter the synthesis of ?-carboline derivatives was studied.At first the biological activity especially anti-tumor activity of?-carboline derivatives was reviewed,then a series of ?-carboline derivatives in which C7 position was substituted by different groups have been synthesized.We used 6-bromoindole as a starting material,through Vilsmeier-Haack reaction to give 3-formyl-6-bromoindole,then 6-bromo-3-(2-nitrovinyl)-indole was obtained by the Knoevenagel reaction.After sodium borohydride and iron monium chloride reduction system to give 6-bromotryptamine,which reacted formaldehyde via Pictet-Spengler reaction to give 7-bromo-1,2,3,4-tetrahydro-1-hydrogen-?-carboline.Finally the target compounds were obtained via Suzuki-Coupling and oxidative dehydrogenation with Pd/C.