Study On Synthesis Of Tetrahydroisoquinolines And Monoamine Oxidase Inhibitory Activity

Monoamine oxidases (MAO) are very important enzymes that cancatalyze the oxidative deamination of a number of monoamines. In humansthere are two separate MAO isoforms (MAO-A, MAO-B), which exhibitdifferent but overlapping substrate. When the activity of MAO becomeabonormal, the monoamines in brain will be oxidized acceleratedly, whichcan cause nervous system disorders.According to the characteristics of MAO, their inhibitors can bedivided into MAO-A inhibitiors, MAO-B inhibitors and non-selectiveMAO inhibitors. MAO-A inhibitors can inhibit the activity of MAO-Areversiblely and selectively, which are used to treat depression. MAO-Binhibitors can inhibit the activity of MAO-B, which are used to treatParkinson’s disease and Alzheimer’s disease.We have designed and synthetized monoamine oxidase inhibitors(MAOIs) and test their MAO activities, the main experiments and results asfollows:1.1-Aminomethyl-1,2,3,4-tetrahy-droisoquinoline(ATIQ) was synthe- sized from phenylethylamine via acylation, amination with phthalimidepotassium, Bisehler-Napieralski cyclization, hydrazine solution, reduction.Its total yield is53.4%, which is about1.5times higher then the literatureyield (36.2%). The route has the features of operating simple, mildconditions, cheap raw materials and so on.2. In the preparing of compound3, we use P2O5dehydrating agentinstead of POCl3, witch simplified the post-processing and the yield stableat about85%.3. The preparation of compound4, we use method of "one-pot",witchsimplified the operation and improved the yield to70%is20%higher thanthe iterature yield (48.3%).4. Designed and synthesized five tetrahydroisoquinoline compoundsand the compounds12,13,14and15are new compounds and theirstructure were confirmed by IR and1HNMR confirmed.5. Preliminary pharmacological test show that the target compoundshave a certain MAO inhibitory activity, wherein the compounds12,13and14can inhibit the MAO-A selectively. Our work will lay a foundationfor studying the MAO inhibitors witch are low toxicity, reversible andselective.