Microbial transformations of steviol and its analogue

• Main Authors: Tsung-Han Yeh, 葉宗翰
• Other Authors: 林淑娟
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/zuqq98

碩士 === 臺北醫學大學 === 藥學系(碩博士班) === 102 === Stevioside is a natural sweetener extracted from the leaves of Stevia rebaudiana (Bertoni) Bertoni possessing many biological activities. Steviol (1) and its analog 3 with ent-kaurene scaffold are derived from stevioside. 1 possesses many biological activities, such as anti-proliferative effect, immunomodulatory effect, and stimulating insulin secretion via an action on ?? cells. Due to possess isoprenoid scaffold, they are suitable for the study of microbial transformation. In order to obtain more ent-kaurene compounds to develop new biological activities, steviol (1) and its analogs 3 are selected as the substrates for microbial transformation. By screening results and reproducility, Mortierella isabellina、Beauveria sulfurescens and Nocardia sp. were selected for microbial transformation of 1 and 3. Incubation of 1 with M. isabellina yielded ent-13,16??,17-trihydroxy-kauran-19-oic acid (4)、5、ent-7??,13-dihydroxy-kaur-16-en-19-oic acid (6), 7, and ent-9??,13-dihydroxy-kaur-16-en-19-oic acid (8). Incubation of 1 with B. sulfurescens afforded 4, ent-13,17-dihydroxy-kaur-15-en-19-oic acid (9), and 10. On the other hand, incubation of 3 with Nocardia sp. produced ent-13-hydroxy-16??-methyl-15-oxokauran-19-oic acid (11), 12, 13, and 14. Incubation of 3 with M. isabellina yielded 2, 11, and 15. Among them, metabolites 5, 7, 10, 13, and 14 are the new compounds. The structures of these new compounds were elucidated by 1D and 2D NMR, and HRTOFMS. Furthermore, the pharmacological testing of these isolated compounds is in progress.