The Main Ingredient In Traditional Chinese Medicine Magnolol Magnolol And Honokiol Microbial Conversion

Microbial transformation is an efficient and key mean for structural modification of organic compounds, especially natural products with complex structures. This approach possesses some advantages over chemical method such as high stereo-and regio-selectivity, environmental benignancy, etc. Most importantly, microbial transformation can carry out some reactions which chemical approach cannot access, and can obtain novel diverse derivatives with higher activities, lower toxicity, and perfect drugability. As a result, microbial transformation has become a significant and efficient approach for structural modification of some compounds.Magnoliae Cortex, the bark of Magnolia officinalis Rhed.(Magnoloaceae) is one of traditional Chinese medicines, which can be used for treatment of gastrointestinal disorders, anxiety and allergic disease. Magnolol and honokiol are two lignans abundantly available exploited in the medicinal plants M. officinalis and M. obovata. They have a wide spectrum of pharmacological activity including anti-tumor, anti-stress, anti-anxiety, anti-inflammation effects. Thus, their structural modification for obtaining new derivatives with better activity and lower toxicity is of interest. In this dissertation, the microbial transformations of these two compounds have been systematically investigated, the results are shown as follows.Thirty-seven fungal strains were employed as biocatalysts for the biotransformations of magnolol and honokiol. By TLC and HPLC-UV analyzing, it was found that five/four filamentous fungi have the capability to transform magnolol, and honokiol, respectively. Three filamentous fungal strains including Cunninghamella echinulata AS3.3400, Absidia coerulea AS3.2462and Rhizopus japonicusa ZW-4show the ability to transform both magnolol and honokiol. Considering the diversity and novelty of the products by LC-UV-MS analyses, C. echinulata AS3.3400and R. japonicus ZW-4were selected candidate strains for the further scale-up transformations.Nine products have been obtained from transformation of magnolol, and ten products from transformation of honokiol by using various chromatographic techniques. The structures of these products were identified on the basis of MS, NMR, UV, IR and CD spectral data analyses.17of them were new compounds. The major reactions include hydroxylation and glycosylation. Their possible biosynthetic pathways were then proposed on the basis of the structural comparison of the products and the investigation of the time courses of the biotransformation.The in vitro anti-tumor, anti-neuroinflammation and neuroprotection bioassay were carried out, the results revealed that some products exhibited potent activity of neuroprotection.