3氧代齐墩果酸及其聚乙二醇缀合物的微生物转化药物分析学医专业论文.docxVIP

AB AB STRACT 3-oxo—olean一1 2一en一28一oic acid(3-oxo—OA)，a kind of pentacyclic trite叩enoid exhibits anticancer and antiangiogenic actiVities．But the weaker biological actiVities and lower wate卜solubility limited its application．The chemical methods are more commonly used than the biotransfonllated procedures fbr modincation．The chemical methods，howeVer， were limited to activated positions in the trite叩enoid molecules．Biotransfonnation，which exhibits higher region-selectiVity and stereo-selectiVity，may contribute to new deriVatiVes of 3一oxo-0A for the research of lead compounds．Here，3一oxo一0A was modi行ed using both chemical synthesis and microbial transfornlation in order to obtain noVellead compounds． The lower water—solub订ity of organic compounds is of problems of the biotransfonnation．The PEGylation can be used fbr s01Ving the wate卜solubility problems in pha咖aceutical research．The 3-oxo—OA was PEGylated in order that 3一oxo—OA dissolVed in the zymotic fluid without any o唱anic cosolVent，Microbial transfonnation of 3-oxo-0A and its PEGylation compound were perf．onned by彳印P曙i，f“s fPr馏淞3．3 93 5 by both the resting and growing cells． The microbial transfomlation conditions of 3-oxo—OA by A驴P曙i，，甜s胞r旭螂3．3935 were optimized．The biotransfbnnation of 3-oxo-0A afbrded four products by growing彳印P曙甜，淞胞r陀淞3．3935，and obtained呐o products by resting A驴P馏i，，“s胞r陀“s 3．3 93 5．The transfornlation of PEGylated 3一oxo—OA afforded one product．The transf．onnated products were deriVatized． The anticancer and 0【一glucosidase inhibito巧 actiV ity of 3一oxo-OA and its transfornlated deriVatiVes were eValuated．The results showed that the ring-cleaVage and the “ng—expansion of A—ring did not af先ct the anticancer actiVity．But the a-glucosidase inhibitory actiVity greatly decreased with A—ring changing． Key Words：3-oxo-OA，Microbialtransfonnation，PEG，anticancer，旺一glucosidase actiVity 万方数据 目 目 录 1 前言 1 1．1聚乙二醇 1 1．1．1聚乙二醇的概述 ．1 1．1．2聚乙二醇修饰药物分子化合物的研究进展 ．1 1．1．3聚乙二醇在微生物转化方面的应用 ．3 1．1．4聚乙二醇在其他方面的应用 ．4 1．2微生