Incense Furans Synthesis And Pharmaceutical Research

Agarowood(Chenxiang) is a precious Chinese traditional medicine. Agarofurans are one structural type of the important contituents of agarowood oil. They were found to be bioactive in pharmacological screening for the neuro-system. In order to study and exploit the bioactivity of these compounds, we planned to modify them chemically. We designed and accomplished the introduction of substituents onto 1,2,3,4,9 positions, especially, studied the substitution at 4-position in detail. 60 agarofurans have been synthesized stereoselectively, of which 42 have not been reported, and 7 are natural products. Stereochemical studies can be exemplified by the application of CD of a benzoate to identify the configurations of 2-OH. The configurations of 3-OH were established via sterically controlled synthesis. Some reactions encountered in the synthetic approaches have been studied, for example, the regioselect ivity of the reductive ring-opening reaction of 3,4-epoxides; the substitution at 4-position and the conversion of diols to agarofurans, etc.. Most compounds have been supplied for pharmacological test on the rodent neuro-system: The bioactivity of these compounds can be grouped into suppression and stimulation. The preliminary Structure-Activity Relationship analysis has been made. In order to explore the process of the metabolism, observe whether the metabolites increase or decrease the activity, which is helpful to further structure modification, we studied the metabolism of the representative compound 1-4 in vitro with liver microsomes from rats. We isolated and tentatively indenfied 6 metabolites. 5 of them were confirmed by the synthesis. In order to obtain some information at the molecular level, using some biophysical techniques (by DSC, FTIR, Raman), studied the interaction between 5 representative compounds with DPPC liposome, the data could be correlated with the results from animal tests. The results might be helpful for further structure modification.