benzyl (4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-13-oxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate | 1391817-31-4

• 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: benzyl (4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-13-oxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate
• CAS: 1391817-31-4
• 化学式: C₃₉H₅₄O₅
• 分子量: 602.855
• InChiKey: TZLXHAYCDZVKAR-PEDVBECTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.64
• 重原子数：
  44.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  69.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  benzyl (4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-13-oxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 11-oxo-oleanolic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

  摘要：

  A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring-fused at C-2, C-3 positions showed a dramatic increase in inhibition, the two most potent PTP1B inhibitors 19 (IC50 = 0.91 mu M) and 21 (IC50 = 0.98 mu M) showed about 3-fold more potent than lead compound OA. Some C-ring modified OA analogs showed high selectivity for PTP1B over TCPTP, among them, 50 possessed the best selectivity of 6.6-fold.

  DOI：

  10.3987/com-12-12445
• 作为产物：
  描述：

  (3β) benzyl 3-acetoxy-olean-11-en-28-oate 在 重铬酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以153 mg的产率得到benzyl (4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-13-oxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

  摘要：

  A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring-fused at C-2, C-3 positions showed a dramatic increase in inhibition, the two most potent PTP1B inhibitors 19 (IC50 = 0.91 mu M) and 21 (IC50 = 0.98 mu M) showed about 3-fold more potent than lead compound OA. Some C-ring modified OA analogs showed high selectivity for PTP1B over TCPTP, among them, 50 possessed the best selectivity of 6.6-fold.

  DOI：

  10.3987/com-12-12445

文献信息

• Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus
  作者：Sumei Li、Xiuhua Jia、Xintian Shen、Zhuwen Wei、Zhiyan Jiang、Yixian Liao、Yiming Guo、Xiaojun Zheng、Guohua Zhong、Gaopeng Song

  DOI：10.1016/j.bmc.2017.06.025

  日期：2017.8

  Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-beta-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC50 values of 4.05 mu M and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3 beta- to 3 alpha-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry. (C) 2017 Elsevier Ltd. All rights reserved.