4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid lactam

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid lactam
• 英文别名: 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam；(4α,8β)-13β-methyl-13α-amino-16-hydroxy-13,16-lactamyl-17-norkauran-18-oic acid；Isosteviol lactam；(1R,4S,5R,9S,10R,13S)-5,9,13-trimethyl-15-oxo-14-azatetracyclo[11.3.1.01,10.04,9]heptadecane-5-carboxylic acid
• 化学式: C₂₀H₃₁NO₃
• 分子量: 333.471
• InChiKey: KGAVVPASANRIHQ-XGBBNYNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid lactam 、 2-甲氧基乙胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  从甜菊醇和异甜菊醇衍生的支架合成面向多样性的图书馆。

  摘要：

  容易获得的天然产物甜菊糖苷提供了独特的二萜核心结构，可通过面向多样性的合成和官能团转换来探索小分子文库的开发。验证阵列由甜菊醇、异甜菊醇和衍生自甜菊苷的相关类似物制备，以产生 90 多种化合物。这些化合物已提交给 NIH 分子库小分子存储库，以便在分子库筛选中心网络中进行筛选。在多个文库成员的多个高通量分析中确定了微摩尔命中。对化合物进行了化学信息学分析，验证了这组化合物的预期多样性和复杂性。

  DOI：

  10.1021/acscombsci.9b00186
• 作为产物：
  描述：

  异甜菊醇 在 吡啶 、 氯化亚砜 、 盐酸羟胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid lactam
  参考文献：
  名称：

  Synthesis and In Vivo Acute Antihyperglycemic Evaluation of Novel Isosteviol Derivatives

  摘要：

  异雌二醇是一种具有多种生物活性的四环双萜类化合物。本文合成了一系列含有 C-18 羧基（5-12）、C-16羰基（14-16）和与异塞维醇结构融合的含杂原子框架（18-19）的新型异塞维醇衍生物，并对其体内急性抗高血糖作用进行了评估。其中，化合物 8 的抗高血糖作用最强。此外，还主要分析了结构-活性关系（SAR）。所有新合成化合物的结构都是通过 1H、13CNMR、MS、IR 和基本分析确定的。

  DOI：

  10.2174/157018010792929522

文献信息

• Stereoselective synthesis of bioactive isosteviol derivatives as α-glucosidase inhibitors
  作者：Ya Wu、Jing-Hua Yang、Gui-Fu Dai、Cong-Jun Liu、Guo-Qiang Tian、Wen-Yan Ma、Jing-Chao Tao

  DOI：10.1016/j.bmc.2009.01.017

  日期：2009.2

  Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors. (c) 2009 Published by Elsevier Ltd.
• Transformation of isosteviol oxime to a lactone under Beckmann reaction conditions
  作者：Olesya I. Militsina、Galina I. Kovyljaeva、Galina A. Bakaleynik、Irina Yu. Strobykina、Vladimir E. Kataev、Vladimir A. Alfonsov、Rashid Z. Musin、Dmitry V. Beskrovny、Igor A. Litvinov

  DOI：10.1070/mc2005v015n01abeh001946

  日期：2005.1

  Heating the 16-E-oxime of isosteviol (ent-16-E-hydroxyiminobeyeran-19-oic acid) with concentrated hydrochloric acid (or 25% H2SO4) at 110 degreesC leads to the formation of lactone of 4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid as the main product, whereas approximately equal quantities of this lactone and lactam of 4alpha-carboxy- 13alpha-amino- 13,16- seco-ent-19 norbeyeran-16-oic acid are formed by heating the 16-E-oxime of isosteviol with concentrated hydrochloric acid in an ampoule at 180 degreesC.
• Transformation of Isosteviol Lactam by Fungi and the Suppressive Effects of Its Transformed Products on LPS-Induced iNOS Expression in Macrophages
  作者：Bo-Hon Chou、Li-Ming Yang、Shwu-Fen Chang、Feng-Lin Hsu、Li-Hsuan Wang、Wen-Kuang Lin、Pan-Chun Liu、Shwu-Jiuan Lin

  DOI：10.1021/np100915q

  日期：2011.6.24

  From the screening of 21 microbial strains, Absidia pseudocylindrospora ATCC 24169 and Aspergillus niger BCRC 32720 were found to reproducibly transform isosteviollactam (4 alpha-carboxy-13 alpha-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam) (3) into various compounds. Preparative-scale transformation of 3 with Abs. pseudocylindrospora yielded two new hydroxylated compounds (4 and 5), with conservation of the lactam ring. Preparative-scale transformation of 3 with Asp. niger afforded seven new compounds, 6 and 9-14, together with the known compounds 7 and 8. A single-crystal X-ray diffraction experiment confirmed the structure of 14. The suppressive effects of compounds 1-14 on the lipopolysaccharide-induced expression of the inducible nitric oxide synthase gene in RAW 264.7 macrophages were examined by a reverse-transcription real-time PCR analysis. With the exception of 7, all other compounds significantly reduced levels of iNOS mRNA relative to control cells, which were induced by LPS alone. Compounds 2, 3, and 5 were similar in activity to dexamethasone, while 9 was more potent.
• Synthesis and In Vivo Acute Antihyperglycemic Evaluation of Novel Isosteviol Derivatives
  作者：Junqing Chen、Xiaoming Zha、Min Sun、Jin Cai、Wen Zhou、Min Ji

  DOI：10.2174/157018010792929522

  日期：2010.11.1

  Isosteviol is a beyerane tetracyclic diterpenoid with a large variety of biological activities. In this article, a series of novel isosteviol derivatives containing the modification of C-18 carboxyl group (5-12), C-16 carbonyl group (14- 16) and heteroatom-containing frameworks fused with isosteviol structure (18-19) were synthesized and evaluated for their in vivo acute antihyperglycemeric effects. Among them, compound 8 exhibited the most potent antihyperglycemeric effects. Furthermore, primarily, structure-activity relationship (SAR) was also analyzed. The structures of all the newly synthesized compounds were determined by 1H, 13CNMR, MS, IR and elementary analysis.

  异雌二醇是一种具有多种生物活性的四环双萜类化合物。本文合成了一系列含有 C-18 羧基（5-12）、C-16羰基（14-16）和与异塞维醇结构融合的含杂原子框架（18-19）的新型异塞维醇衍生物，并对其体内急性抗高血糖作用进行了评估。其中，化合物 8 的抗高血糖作用最强。此外，还主要分析了结构-活性关系（SAR）。所有新合成化合物的结构都是通过 1H、13CNMR、MS、IR 和基本分析确定的。
• Diversity-Oriented Library Synthesis from Steviol and Isosteviol-Derived Scaffolds
  作者：Trinh A. D. Holth、Michael A. Walters、Oliver E. Hutt、Gunda I. Georg

  DOI：10.1021/acscombsci.9b00186

  日期：2020.3.9

  for small molecule library development by diversity-oriented synthesis and functional group transformations. Validation arrays were prepared from steviol, isosteviol, and related analogues, derived from stevioside, to produce over 90 compounds. These compounds were submitted to the NIH Molecular Libraries Small Molecule Repository for screening in the Molecular Libraries Screening Center Network. Micromolar

  容易获得的天然产物甜菊糖苷提供了独特的二萜核心结构，可通过面向多样性的合成和官能团转换来探索小分子文库的开发。验证阵列由甜菊醇、异甜菊醇和衍生自甜菊苷的相关类似物制备，以产生 90 多种化合物。这些化合物已提交给 NIH 分子库小分子存储库，以便在分子库筛选中心网络中进行筛选。在多个文库成员的多个高通量分析中确定了微摩尔命中。对化合物进行了化学信息学分析，验证了这组化合物的预期多样性和复杂性。