2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl-(1→4)-2,3,6-tri-O-benzoyl-1-(4-tolyl)thio-β-D-glucopyranoside | 1412198-57-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl-(1→4)-2,3,6-tri-O-benzoyl-1-(4-tolyl)thio-β-D-glucopyranoside
• 英文别名: [(2R,3R,4S,5R,6S)-4,5-dibenzoyloxy-6-(4-methylphenyl)sulfanyl-3-[(2S,3R,4R,5S,6S)-3,4,5-tribenzoyloxy-6-methyloxan-2-yl]oxyoxan-2-yl]methyl benzoate
• CAS: 1412198-57-2
• 化学式: C₆₁H₅₂O₁₅S
• 分子量: 1057.14
• InChiKey: WLGUJUFUVLWNSJ-WOIAIAIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  77
• 可旋转键数：
  23
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  211
• 氢给体数：
  0
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  6α-O-benzoyl chlorogenin 、 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl-(1→4)-2,3,6-tri-O-benzoyl-1-(4-tolyl)thio-β-D-glucopyranoside 在 N-碘代丁二酰亚胺 、 silver trifluoromethanesulfonate 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以320 mg的产率得到[(2R,3R,4S,5R,6R)-4,5-dibenzoyloxy-6-[(1R,2S,4S,5'R,6R,7S,8R,9S,12S,13R,16S,18S,19S)-19-benzoyloxy-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane]-16-yl]oxy-3-[(2S,3R,4R,5S,6S)-3,4,5-tribenzoyloxy-6-methyloxan-2-yl]oxyoxan-2-yl]methyl benzoate
  参考文献：
  名称：

  Discovery of the First Series of Small Molecule H5N1 Entry Inhibitors

  摘要：

  The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Inhibition of H5N1 entry into cells may be an effective strategy. We report the first three small molecule inhibitors saponins with 3-O-beta-chacotriosyl residue, which Showed potent inhibitory activity with IC50 of 7.22-9.25 mu M. The subsequent SAR studies showed the 3-O-beta-chacotriosyl residue was essential for the activity, and the aglycone structure also affected the activity.

  DOI：

  10.1021/jm900275m
• 作为产物：
  描述：

  2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyltrichloroacetimidate 、 p=methylphenyl 2,3,6-tri-O-benzoyl-1-thio-β-D-glucopyranoside 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl-(1→4)-2,3,6-tri-O-benzoyl-1-(4-tolyl)thio-β-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Analogs of Methyl Ursolate 3-O-β-Chacotrioside as H5N1 Viral Entry Inhibitors

  摘要：

  The earliest stage of influenza virus infection is the viral entry to the host cell. In our previous work, we discovered the first three small molecule H5N1 viral entry inhibitors 1-3. Here, based on saponin 3, methyl ursolate 3-O-beta-chacotrioside, several analogs were synthesized and evaluated to understand the structure-activity relationships of this type of compound on the H5N1 viral entry inhibitory activity. The preliminary studies demonstrated that unlike saponins 1 and 2, it is possible to reduce the 3-O-chacotriosyl residue of compound 3 to a disaccharide without affecting the viral entry activities significantly. The results obtained will render new clues to the understanding of the antiviral profile for these types of compounds.

  DOI：

  10.1080/07328303.2012.687060

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.