Preparation of spirostan-type derivatives from diosgenin

• Main Authors: Yi-Jing Lin, 林宜靜
• Other Authors: 林淑娟
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/kxrj67

碩士 === 臺北醫學大學 === 藥學系(碩博士班) === 102 === 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.