| 摘要: | Isosteviol為甜菊主要成分stevioside之水解產物。根據文獻記載具有降血壓、降血糖、抗發炎、抗菌和腫瘤等生物活性，過去曾有isosteviol經微生物轉換之衍生物被報導，但因轉換率不高無完整探討結構與活性之關係。本實驗室利用化學修飾法來進行isosteviol C16和C19等化學部位之結構修飾，並探討其生物活性，以尋求作藥物開發之先導化合物。 實驗中，已合成出C16-hydrazone衍生物105、 acyl amine衍生物106-113和amine衍生物115等10個化合物。另一方面，isosteviol C19之修飾，亦已合成出amide衍生物114、116、227、119和120、ether衍生物121、ester衍生物122共7個化合物。在activation AMPK in C2C12 cells實驗初步得知衍生物HSU-STD 012和HSU-STD 004在P-AMPK/T-AMPK 比值與AMPK活化比對照組AICAR比較活性高出4.2%和12%；而從activation glucose uptake in C2C12 cells之實驗中，則是以loperamid作正向對照組 (positive contol)，根據實驗數據得知衍生物HSU-STD 001 (114.54 ± 0.95)、HSU-STD 003 (114.28 ± 0.56)和HSU-STD 004 (115.38 ± 1.45)較好，衍生物HSU-STD 015 (111.28 ± 0.66)和HSU-STD 023 (107.76 ± 1.07)次之。
Isosteviol is obtained from acid hydrolysis of stevioside. Isosteviol have many biological activities including anti-hypertension, anti-hyperglycemic, anti-inflammatory, anti-bacteria and anti-tumor. The microbial transformation of isosteviol has studied, however, to date, the yield of isosteviol derivatives were too low. Herein, we proposed two structure-modified isosteviol on C16 and C19 and their activities were also investigated. In the synthetic classification, we have synthesized 10 of C16 isosteviol derivatives to obtaining C16-hydrazone 105, C16-amine 106-113, 115, respectively. Next, the chemical modification 7 derivatives on C19, we have synthesized a series of amide derivatives of 114, 116, 117, 119 and 120. It is important to note that 121 was using LiALH4 as a reductant to reduct C19-COOH and C16 ketone group, and ester derivative 122 was synthesized by using a benzyl bromide as an electrophile reagent. In activation 5’-AMP-activated protein kinase (AMPK) in myoblast cells (C2C12) test, of these compounds, the No.HSU-STD 012 and the HSU-STD 004 has better activity than aminoimidazole carboxamide ribonucleotide (AICAR). In test of glucose up-take activity, HSU-STD 001 (114.54 ± 0.95), HSU-STD 003 (114.28 ± 0.56)and HSU-STD 004 (115.38 ± 1.45) are attributed to the first-class and HSU-STD 015 (111.28 ± 0.66) and HSU-STD 023 (107.76 ± 1.07)are attributed to the second- class. |
