ent-7α-hydroxy-16-ketobeyeran-19-oic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ent-7α-hydroxy-16-ketobeyeran-19-oic acid
• 英文别名: 7β-hydroxyisosteviol；7-beta-Hydroxyisosteviol；(1S,2S,4S,5R,9S,10S,13S)-2-hydroxy-5,9,13-trimethyl-14-oxotetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylic acid
• 化学式: C₂₀H₃₀O₄
• 分子量: 334.456
• InChiKey: RARHTOIMTZCWKS-SWTLLTDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  甜菊糖 在 盐酸 、 Cunninghamella bainieri (UI 3065) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 146.0h， 生成 ent-7α-hydroxy-16-ketobeyeran-19-oic acid
  参考文献：
  名称：

  Microbial Transformations of Isosteviol

  摘要：

  Microbial transformations of the tetracyclic diterpenoid isosteviol (ent-16-ketobeyeran-19-oic acid) (2) have revealed that isosteviol is metabolized by Cunninghamella, bainieri, Actinoplanes sp., Mucor recurvatus, and Cunninghamella blakesleeana to yield five new metabolites, ent-11alpha,12alpha-dihydroxy-16-ketobeyeran-19-oic acid (5), ent-11alpha,12alpha,17-trihydroxy-16-ketobeyeran-19-oic acid (6), ent-12alpha,15alpha-dihydroxy-16-ketobeyeran-19-oic acid (7), ent-7alpha,15alpha-dihydroxy-16-ketobeyeran-19-oic acid (8), and ent-9alpha-hydroxy-16-ketobeyeran-19-oic acid (9), together with three known metabolites, ent-7alpha-hydroxy-16-ketobeyeran-19-oic acid (3), ent-7beta-hydroxy-16-ketobeyeran-19-oic acid (4):, and ent-12alpha-hydroxy-16-ketobeyeran-19-oic acid (10). The structures of these metabolites were established on the basis of HRFABMS and 1D and 2D NMR spectral data. In addition, metabolites 3-10 were tested for antihypertensive activity and were found to be less active than the parent compound 2.

  DOI：

  10.1021/np000622y

文献信息

• Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor
  作者：Bo-Hon Chou、Li-Ming Yang、Shwu-Fen Chang、Feng-Lin Hsu、Chia-Hsin Lo、Wen-Kuang Lin、Li-Hsuan Wang、Pan-Chun Liu、Shwu-Jiuan Lin

  DOI：10.1016/j.phytochem.2009.03.015

  日期：2009.4

  A number of hydroxylated diterpenoids were obtained from the microbial transformation of isosteviol lactone (4 alpha-carboxy-13 alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) (2) with Mucor recurvatus MR 36, Aspergillus niger BCRC 31130, and Absidia pseudocylindrospora ATCC 24169. Incubation of 2 with M. recurvatus and Asp. niger led to isolation of seven known compounds (1 and 3-8). Incubation of 2 with Abs. pseudocylindrospora produced 5 and six previously unreported compounds (9-14). The structures of these isolated compounds were deduced by high-field NMR techniques (H-1, C-13, DEPT, COSY, NOESY, HSQC, and HMBC), and those of 9 and 11 were further confirmed by X-ray crystallographic analyses. Subsequently, the inhibitory effects on activator protein-1 (AP-1) activation in lipo-polysaccharide-stimulated RAW 264.7 macrophages of all of these compounds were evaluated. Compounds 2-5, 8, 9, 11, and 12 exhibited significant inhibitory activity, while 3 was more potent than the reference compound of dexamethasone. (C) 2009 Elsevier Ltd. All rights reserved.
• Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors
  作者：Yoshiyuki Mizushina、Toshihiro Akihisa、Motohiko Ukiya、Yusuke Hamasaki、Chikako Murakami-Nakai、Isoko Kuriyama、Toshifumi Takeuchi、Fumio Sugawara、Hiromi Yoshida

  DOI：10.1016/j.lfs.2005.03.022

  日期：2005.9

  Isosteviol (ent-16-ketobeyeran-19-oic acid) is a hydrolysis product of stevioside, which is a natural sweetener produced in the leaves of Stevia rebaudiana (Bertoni) Bertoni. In this report, we prepared isosteviol and related compounds from stevioside by microbial transformation and chemical conversion and assayed the inhibitory activities toward DNA metabolic enzymes and human cancer cell growth. Among twelve compounds obtained, only isosteviol (compound 3) potently inhibited both mammalian DNA polymerases (pols) and human DNA topoisomerase II (topo II), and IC50 value for pol alpha was 64.0 mu M. This compound had no inhibitory effect on higher plant (cauliflower) pols, prokaryotic pols, human topo I, and DNA metabolic enzymes such as human telomerase, T7 RNA polymerase, and bovine deoxyribonuclease I. With pol alpha, isosteviol acted non-competitively with the DNA template-primer and nucleotide substrate. Isosteviol prevented the growth of human cancer cells, with LD50 values of 84-167 mu M, and 500 mu g of the compound caused a marked reduction in TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation (inhibitory effect, 53.0%). The relationship between the structure of stevioside-based compounds and these activities were discussed. (c) 2005 Elsevier Inc. All rights reserved.
• Biotransformation of dihydroisosteviol and the effects of transformed products on steroidogenic gene expressions
  作者：Shwu-Fen Chang、Li-Ming Yang、Tsurng-Juhn Huang、Chin-Yang Chen、Shiow-Yunn Sheu、Pan-Chun Liu、Shwu-Jiuan Lin

  DOI：10.1016/j.phytochem.2013.07.015

  日期：2013.11

  The biotransformation of dihydroisosteviol with Absidia pseudocylindrospora ATCC 24169, Streptomyces griseus ATCC 10137, Mucor recurvatus MR36, and Aspergillus niger BCRC 31130 yielded 15 metabolites, eight of which were previously unknown. Structures of metabolites were established by 2D NMR techniques and HRMS data, two of which were further corroborated by chemical means, and another via single-crystal X-ray diffraction analysis. Subsequently, two steroidogenic cell lines (Y-1 mouse adrenal tumor and MA-10 mouse Leydig tumor cells) were used in a reverse transcription-PCR analysis to assess the effects of all compounds on steroidogenic gene expressions using forskolin as a positive control. The tested gene expressions included steroidogenic factor-1 (SF-1), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450SCC) enzyme. Gene expression profiles showed that ten of the tested compounds effectively suppressed P450(SCC) mRNA expression in both Y-1 and MA-10 cells. Several induced SF-1 gene expression and two enhanced StAR gene expression in Y-1 cells. By contrast, in MA-10 cells, one compound effectively suppressed StAR mRNA expression, whereas for others effectively suppressed SF-1 gene expression. The results suggest that analogs of dihydroisosteviol can be potential modulators to alter steroidogenic gene expressions and subsequent enzyme activities. (C) 2013 Elsevier Ltd. All rights reserved.
• Microbial Transformations of Isosteviol
  作者：Feng-Lin Hsu、Chia-Chung Hou、Li-Ming Yang、Juei-Tang Cheng、Tzong-Cherng Chi、Pang-Chun Liu、Shwu-Jiuan Lin

  DOI：10.1021/np000622y

  日期：2002.3.1

  Microbial transformations of the tetracyclic diterpenoid isosteviol (ent-16-ketobeyeran-19-oic acid) (2) have revealed that isosteviol is metabolized by Cunninghamella, bainieri, Actinoplanes sp., Mucor recurvatus, and Cunninghamella blakesleeana to yield five new metabolites, ent-11alpha,12alpha-dihydroxy-16-ketobeyeran-19-oic acid (5), ent-11alpha,12alpha,17-trihydroxy-16-ketobeyeran-19-oic acid (6), ent-12alpha,15alpha-dihydroxy-16-ketobeyeran-19-oic acid (7), ent-7alpha,15alpha-dihydroxy-16-ketobeyeran-19-oic acid (8), and ent-9alpha-hydroxy-16-ketobeyeran-19-oic acid (9), together with three known metabolites, ent-7alpha-hydroxy-16-ketobeyeran-19-oic acid (3), ent-7beta-hydroxy-16-ketobeyeran-19-oic acid (4):, and ent-12alpha-hydroxy-16-ketobeyeran-19-oic acid (10). The structures of these metabolites were established on the basis of HRFABMS and 1D and 2D NMR spectral data. In addition, metabolites 3-10 were tested for antihypertensive activity and were found to be less active than the parent compound 2.