The Research On Synthesis And Biological Activity Of 2-aryl-2-morpholinols

So far, the morpholinol compounds is known to have various functions and bioactivities such as antidepressant and antibacterial, which is getting attention by its treatment effective and opposite small side effect. It has been one of the directions to prevent and cure depression. According to research situation of morpholinol compounds, the new compounds synthesized by modification of 2-aryl-2-morpholinol structure.The aim of this dissertation is to synthesizes and screens 2-aryl-2-morpholinol with antidepressant active or antibacterial active, to provides the lead compounds for the new medicine. The major research contents are described as follows:(1)Retains the manufacture of 2-aryl-2-morpholino, we won seven new 2-aryl-2- morpholinol by bring the new substituent to the aromatic rings.The target compounds structure after IR, 1HNMR corroboration.(2)Design routes of synthetic 2-aryl-2-morpholinol hydrochloride with 2-aminopropanol. We got the target compound by four step reactions: Friedel-Crafts acylation, arylketones ofα-bromination, ammonification and acidification, and some reaction conditions has been optimized. The results showed the synthesis reaction is high selectivity, mild reaction conditions and high yield. The reaction of the average gross admission rate of 74.2 %.(3)The research uses N-dimethyl formamide to replace acetonitrile,pyridine, acetone and other solvents, can improve the reparation conditions of morpholinol,lower temperatures and quickly get to the target product.(4)We established a"behavioral despair"model by Porsolt forced swimming test in mice to evaluate and screen antidepressant activity of compunds from the target product.The result showed that 2-(2-fluorophenyl)-3,5-dimethyl-2-morpholinol hydrochloride get from D-2-aminopropanol,which compared to the blank control could significantly shorten mice immobility time in FST.The result suggested that this compound has good antidepressant effects, maybe is the new lead compounds in antidepressant drug, which makes sure that the compound is worth of research. The antidepressant activity experiment data also showed that target products from different Chiral source had different biological activity.(5)2-aryl-2-morpholinol hydrochloride compounds were examined for antimicrobial activities against Fschevichia coil, Staphylococcus aureus and Salmonella by the paper method. The result showed that 2-(4-tert butylphenyl)-3,5-dimethyl-2-morpholinol hydrochloride has certain antibacterial activity, its minimum inhibition concentration (MIC) was 0.625 g L-1.