Tetrahydro Berberine Compounds Stepholidine Synthetic Research

Alkaloids, widely found in natural plants, animals, microorganisms, have important biological activities. Many of them have been used as common drugs in the clinic. L-stepholidine (l-SPD), a kind of the tetrahydroprotoberberine (THPBs) alkaloids, was used as analgesic in the clinic. Under the basis of the research by Professor Guozhang Jin, Shanghai Institute of Materia Medica first found that l-spd had dual D1 receptor agonist and D2 receptor antagonist actions, which is consistent with the new theory of the pathogenesis of schizophrenia. Such actions may be beneficial for the treatment of schizophrenia. THPBs are structurally different from all known antipsychotic drugs. The synthesis of SPD, therefore, merits further investigation.The synthesis of SPD has been in-depth studied in the paper. An important intermediate has first been reported in detail. In this paper, the procedure optimized is mainly on the steps of Pictet-Spengler aminomethylation, the synthesis of phenylacetic acid derivatives and recrystallisation. Through variety explorations of the reaction conditions, we have found a synthetic method which could obtains higher yield and simplify the manipulation.In the exploration of the experiment, we also got some synthetic regularities and methods of the tetrahydroprotoberberine (THPBs) alkaloids. It is beneficial for further research of the synthesis.Because of the factors of environmental pollution and industrialization, in the synthesis of the tetrahydroprotoberberine(THPBs), we choosed some suitable solvents and reaction conditions.