從薯蕷皂苷元製備spirostan-type衍生物

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Title:	從薯蕷皂苷元製備spirostan-type衍生物 Preparation of spirostan-type derivatives from diosgenin
Authors:	林宜靜 Lin, Yi-Jing
Contributors:	林淑娟
Keywords:	微生物轉換;薯蕷皂苷;元 Microbial transformation;Diosgenin
Date:	2014-07-02
Issue Date:	2019-09-09 11:24:24 (UTC+8)
Abstract:	薯蕷皂苷元(1) [(diosgenin, (25R)-spirost-5-en-3beta-ol)]為steroidal sapogenin中最重要的一個，並且具有廣泛生物活性。此外，文獻指出植物及海洋無脊椎動物中有許多polyhydroxysteroids、sapogenin及其衍生物，並發現其具有良好生物活性。然而選擇性引入如氫氧基的極性官能基於多環化合物較困難，因此利用微生物轉換技術所具有的位置及立體選擇特性進行反應，已成為近年來化學反應的另一替代工具。為了得到具polyhydroxy的spirostan化合物，本研究將薯蕷皂苷元(1)先經由化學半合成得到受質(2)，接著進行微生物轉換研究。經由15株菌種篩選後，選擇Streptomyces griseus及Bacillus megaterium進行大量發酵培養，經抽取、分離、純化得到化合物 3-11，其中受質2經由與S. griseus反應得到3-6；受質2經由與B. megaterium反應得到3、4、9-11。此外，利用微生物轉換所得主代謝產物3為起始原料，以化學半合成得到化合物12-30。所得化合物經由核磁共振光譜及高解析質譜鑑定其結構；化合物藥理活性試驗目前正在進行中。 Diosgenin [(25R)-spirost-5-en-3beta-ol)] (1) is one of the most important steroidal sapogenin. A wide array of new biological activities of diosgenin have been published. In addition, polyhydroxysteroids, sapogenin and their derivatives are commonly found from plants and in marine invertebrates, which exhibit activities against certain diseases. However, it is difficult to introduce polar functional groups such as hydroxyl group into polycyclic compounds. Therefore, microbial transformation has become an alternative tool for structurally modifying natural and synthetic compounds due to its significant regio- and stereoselectivities. In order to obtain polyhydroxyl derivatives with spirostanic skeleton, we first prepare 2 from diosgenin, and then use it as a substrate for microbial transformation. By screening fifteen microorganisms, Streptomyces griseus and Bacillus megaterium were selected for the preparative-scale biotransformation of 2. Preparative-scale fermentation of 2 with S. griseus produced 3-6. Preparative-scale fermentation of 2 with B. megaterium produced 3, 4, 9-11. Furthermore, compound 3 is used as the starting material for the semi-synthesis spirostanes 12-30. Structures of all compounds were established on the basis of NMR and HRTOFMS. Besides, the pharmacological testing of these analogues is in progress.
Description:	碩士指導教授-林淑娟委員-陳國棟委員-鄭可大
Data Type:	thesis
Appears in Collections:	[School of Pharmacy] Dissertation/Thesis

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