Preparation Of Berberine Derivatives And Reseach Of Its Neurotrophic Activity

Berberine, a quaternary ammonium type isoquinoline alkaloid contained in the plant of Rutaceae and Berberidaceae, has significant bioactivity of bactericidal,antibacterial and anti-inflammation. The plants containing berberine have been used in traditional chinese medicine for hundreds years in our country. In recent years, many researches have found not only berberine has significant bioactivity, but also its derivative (tetrahydroberberine, THHB) has significant bioactivity of antioxidation, anti-apoptosis and antiarrhythmic. To reveal the clinical application value of THB, in our research, we synthesized resolution agent((+)-DPT, (-)-DPT) using Industrial Use tartaric acid as raw material, and prepared (+)-13aR-THB, (-)-13aS-THB, 9-OH-THB, (-)-DPT-(+)-13aR-THB, (+)-DPT-(-)-13aS-THB and (+)-DPT-(-)-13aS-THB2 successfully. Among these six compounds, (+)-DPT-(-)-13aS-THB2 is a single crystal. We identified the spatial structure of this compond by X-ray and researched the neurotrophic activityof these six compounds using PC12 cells. The result of X-ray crystal diffraction of (+)-DPT-(-)-13aS-THB2 shows that there is no hydrogen bond between (+)-DPT and (-)-13aS-THB, and there is weak non-conventional interaction between the hydroxyl oxygen of the carboxyl and hydrogen of the C13 of the two (-)-13aS-THB. At the same time, we can find the rings B,C of two S(-)THB are all half-chair conformations. This molecular structure is firstly reported in our research.The result of neurotrophic activity of these six compounds show that the conformations of 13-C of the THB plays a key effect on its neurotrophic activity and the S conformation is its effective conformation. Meanwhile, we can find the substituent on 9-C play a main effect on its neurotrophic activity. In our research, when the–OCH3 of 9-C is substituted by–OH, THB lossed the neurotrophic activity and show cytotoxic activity.