Structural diversification of chemical constituents from bryophytes and their antifungal virulent effects

【作者】 Bin Sun； Jiao-Zhen Zhang； 娄红祥；

【Author】 Bin Sun;Jiao-Zhen Zhang;Hong-Xiang Lou;Key Laboratory of Natural Products & Chemical Biology,Ministry of Education,School of Pharmaceutical Sciences,Shandong University;

【机构】 Key Laboratory of Natural Products & Chemical Biology,Ministry of Education,School of Pharmaceutical Sciences,Shandong University；

【摘要】 Natural products played a key role in the drug discovery^[1,2].During these years,it was found that the diversification of natural products was very important for the drug development^[3].Based on the long-term research of natural products from the bryophyte,our present investigation is to diversify bryophyte-derived compounds（such as biflavone,diterpenoids and bisbibenzyls） by chemical engineering,photo-driven chemical conversion or total synthesis.Firstly,the antifungal compounds were obtained from the bryophyte extracts efficiently by the bio-test guided separation.Secondly,the flavones in the extracts were diversified rapidly by the chemical engineering method,especially,through the reaction with hydrazine as well as its derivatives to obtain pyrazoles,or by the Mannich reaction with secondary amines to give alkaloid derivatives.Thirdly,a series of novel compounds were prepared from diterpenoides in the bryophyte by the photo-driven rearrangement or [2+2] cycloaddition.Finally,four bisbibenzyls were obtained by the total synthesis and diversified by the alkylation,Mannich reaction or bromination.All these novel derivatives were assayed by the method based on the virulence factors-targeting,which was related to the formation of hyphae,biofilm and drug resistance in the invasion process.更多还原

【Abstract】 Natural products played a key role in the drug discovery^[1,2].During these years,it was found that the diversification of natural products was very important for the drug development^[3].Based on the long-term research of natural products from the bryophyte,our present investigation is to diversify bryophyte-derived compounds（such as biflavone,diterpenoids and bisbibenzyls） by chemical engineering,photo-driven chemical conversion or total synthesis.Firstly,the antifungal compounds were obtained from the bryophyte extracts efficiently by the bio-test guided separation.Secondly,the flavones in the extracts were diversified rapidly by the chemical engineering method,especially,through the reaction with hydrazine as well as its derivatives to obtain pyrazoles,or by the Mannich reaction with secondary amines to give alkaloid derivatives.Thirdly,a series of novel compounds were prepared from diterpenoides in the bryophyte by the photo-driven rearrangement or [2+2] cycloaddition.Finally,four bisbibenzyls were obtained by the total synthesis and diversified by the alkylation,Mannich reaction or bromination.All these novel derivatives were assayed by the method based on the virulence factors-targeting,which was related to the formation of hyphae,biofilm and drug resistance in the invasion process.更多还原