Design And Synthesis Of Tetrahydroisoquinoline Compounds

The development of antitussive agents was summarized,and the antitussive action of Nascopine was introduced in detail in this thesis.Based upon the known SAR results,here designed and synthesized three kinds of monobenzyl-1,2.3,4-tetra-hydroiso-quinolines via simplification and modification of Noscapine to search for new chemical entities with antitussive or adrenomimetic activities.Fifteen target compounds,including twelve chiral compounds via asymmetric induction and three racemic ones were obtained,and nine of them have not yet been reported in literatures.The structures of them were determined by ~1HNMR and ESI-MS.The important point and difficulty of this work laid on the construction of 1,2,3.4-tetra-hydroisoquinoline ring and the induction of C-1 chiral center therein.Usingα-phenylethylamine as optical auxiliary,lots of substrates were tried in various conditions for stereoselective Pictet-Spengle or Bischler-Napieralski reaction.Eventually.it was found that the amount and position of electron donating groups on the aryl-ring of arylethylamine part.and the existence of electron withdraw substituents on N-atom were two critical factors for the performance of the reaction.It was found that the synthesized compounds via Bischler-Napieralski reaction induced byα-phenylethylamine had high enantiomeric excess and good optical purity due to the easy isolation of the diastereoisomers by,recrystallization.This methodology will be helpful for the study.Further researches are now under investigation.