Structural Modification Of Curcumol

Curcuma oil is the active ingredient of curcuma which is a traditional Chinese medicine. It has anti-tumor, anti-virus, anti-inflammatory and other functions. Curcumol is one of the active ingredients of curcuma oil. It is a promising anticancer drug. Up to now, there are few reports on structural modification of curcumol by organic methods.In this paper, we study the aromatization of curcumol under acidic conditions. Aromatization of curcumol with acetone is selected as the model reaction in this paper. Hydrobromide is selected as catalyst and tetrahydrofuran as solvent. Based on model reaction, a series of new trienone compounds have been prepared by curcumol reacting with different carbonyl compounds in the yield of 40.3-75.0%. And we proposed mechanism of aromatization. Three trienone compounds'X-ray diffraction data are analyzed. During the study of mechanism, we find that:the stability of carbonium generated from the carbonyl compounds and steric hindrance are the main factors affecting the aromatization. Carbonyl compounds with lower activity and larger steric can not have aromatization with curcumol.In our study, the structural modification of curcumol is also carried out by hydrogenation, rearrangement, oxidation and ring opening reaction. We got hydrogenated curcumol (compound 11), open loop product of curcumol(compound 13),9,10-epoxide(compound 14) and 9-hydroxy derivatives(compound 15), etc. And in the process of structural modification of curcumol, we find that the double bond of curcumol can migrate into the ring under catalysis of potassium hydroxide. After improving the reaction conditions, we get a higher yield of 93.0%. Three-dimensional configuration of compound 12 and 15 is determined based on X-ray diffraction data analysis. We have a thorough discussion of the epoxidation and ring opening reaction mechanism and stereochemistry.