Synthesis Of Nitro Substituted 1,2,3,4-Tetrahydroisoquinoline And Its Derivatives

1,2,3,4-tetrahydroisoquinoline,isreferred to as tetrahydroisoquinoline.Its derivatives,an important class of alkaloids,are widely spreadin the nature.Some of the tetrahydro isoquinoline derivatives have been widely used in clinical as drugs.With thedeepening of the researches on tetrahydroisoquinoline alkaloids,more and more new biological activities,new mechanismsand targets have been discovered and revealed,and the diversities of their biological activities have been paid great attention.In the last five years,studies on activities and mechanisms of tetrahydroisoquinoline compounds in anti-tumor,antibacterial,antiviral,anti-inflammatory,anticoagulant,bronchodilation and central nervous system,have made great progress,and provide ideas and revelation for their activities,and provide the basis for searching lead compounds and rational design of drug molecules.There were four classes of nitro substituted 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized,includingN-substituted 5-nitro-,6-nitro,7-nitro-and 8-nitro-1,2,3,4-tetrahydroisoquinolines.N-substituents were imidazoles,triazoles and piperidines.All the compounds were novel structures and were confirmed by 1HNMR,13CNMR and MS.N-Substituted-5-Nitro-1,2,3,4-tetrahydroisoquinolines were synthesized from isoquinoline as a starting material via four steps including nitration,reduction andHofmann alkylation.N-Substituted-6-Nitro-1,2,3,4-tetrahydroisoquinolines were obtained by cyclization of Pomeranz-Fritsch reaction,reduction and Hofmann alkylation from p-nitrobenzylammonium hydrochlorideas a starting material via there steps.N-Substituted-7-Nitro-1,2,3,4-tetrahydroisoquinolines were synthesized by cyclizationof p-nitrophenylethylamine hydrochloride and formaldehyde via Pictet-Spengler reaction,and Hofmann alkylation.N-substituted-8-nitxo-1,2,3,4-tetrahydroisoquinolines was prepared from 1,2,3,4-tetrahydroisoquinoline as a starting material via five steps,including bromination in 5-C,nitration in 8-C,debromination andreduction of N heterocycle of isoquinoline,Hofmann alkylationin sequence.Paper innovation:1.The successful synthesis of 20 tetrahydroisoquinoline derivatives has not been reported in the literature,and their chemical structures have been confirmed,enriching the compound database,which provides the premise for the study of the activity of this series of compounds..2.The synthesis of 6-nitro-1,2,3,4-tetrahydroisoquinoline was improved,and the yield was greatly improved.3.The intermediate route of 8-nitro-1,2,3,4-tetrahydroisoquinoline was improved,the reaction route was shortened and the yield was improved.