2,3,4-tri-O-acetyl-D-rhamnopyranosyl trichloroacetimidate | 1338925-54-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,4-tri-O-acetyl-D-rhamnopyranosyl trichloroacetimidate
• CAS: 1338925-54-4
• 化学式: C₁₄H₁₈Cl₃NO₈
• 分子量: 434.658
• InChiKey: CBEDSVQSHODOKN-IXZKJPGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.89
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  121.21
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2,3,4-tri-O-acetyl-D-rhamnopyranosyl trichloroacetimidate 、 3β-O-(3,6-di-O-pivaloyl-β-D-glucopyranosyl)olean-12-en-28-oic acid benzyl ester 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2017.06.025

文献信息

• Synthesis and Characterization of the Arylomycin Lipoglycopeptide Antibiotics and the Crystallographic Analysis of Their Complex with Signal Peptidase
  作者：Jian Liu、Chuanyun Luo、Peter A. Smith、Jodie K. Chin、Malcolm G. P. Page、Mark Paetzel、Floyd E. Romesberg

  DOI：10.1021/ja207318n

  日期：2011.11.9

  of antibiotics inhibits bacterial type I signal peptidase and is comprised of three related series of natural products with a lipopeptide tail attached to a core macrocycle. Previously, we reported the total synthesis of several A series derivatives, which have unmodified core macrocycles, as well as B series derivatives, which have a nitrated macrocycle. We now report the synthesis and biological

  天然产物（包括抗生素）的糖基化通常在确定它们的物理特性和生物活性以及它们作为候选药物的潜力方面起着重要作用。芳霉素类抗生素抑制细菌 I 型信号肽酶，由三个相关系列的天然产物组成，脂肽尾连接到核心大环。之前，我们报道了几种具有未修饰核心大环的 A 系列衍生物和具有硝化大环的 B 系列衍生物的全合成。我们现在报告脂糖肽芳霉素变体的合成和生物学评估，其大环用脱氧-α-甘露糖取代基糖基化，并且在某些情况下也被羟基化。带有每种可能的脱氧-α-甘露糖对映体的衍生物的合成使我们能够确定天然产物中糖的绝对立体化学，并表明虽然糖基化不会改变抗菌活性，但它似乎确实提高了溶解度。脂糖肽芳霉素与其信号肽酶靶标结合的晶体结构研究揭示了抑制作用的分子相互作用，并且甘露糖从结合位点被引导到溶剂中，这表明可以在同一位置进行其他修饰以进一步增加溶解度从而减少蛋白质结合并可能优化支架的药代动力学。