6-acetyl-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | 1151668-58-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-acetyl-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one
• 英文别名: 6-Acetyl-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-benzo[1,2-b:3,4-ba(2)]dipyran-8-one；6-acetyl-5-hydroxy-2,2-dimethyl-10-propylpyrano[2,3-f]chromen-8-one
• CAS: 1151668-58-4
• 化学式: C₁₉H₂₀O₅
• 分子量: 328.365
• InChiKey: FELPGGPDDRWOFP-UHFFFAOYSA-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：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-acetyl-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 以83%的产率得到5-hydroxy-6-(1-(hydroxyimino)ethyl)-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one
  参考文献：
  名称：

  Scaffold-hopping strategy toward calanolides with nitrogen-containing heterocycles

  摘要：

  （+)-Calanolide A是首个被确认为对HIV-1和结核杆菌（Mtb）有效的天然产物。在设计针对(+)-calanolide A的结构改进方案时，我们采用了“结构跳板”策略，专注于通过替代环D来合成各种新型的含氮杂环（五元或六元），这有助于进一步揭示其构效关系。 (C) 2013 Gang Liu. 本文由Elsevier B.V.代表中国化学会出版。保留所有权利。

  DOI：

  10.1016/j.cclet.2013.03.007
• 作为产物：
  描述：

  5,7-二羟基-4-丙基香豆素 在 吡啶 、 aluminum (III) chloride 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 6-acetyl-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one
  参考文献：
  名称：

  N-Oxide heterocycles and imidazoles replacing ring D of calanolides against Mycobacterium tuberculosis

  摘要：

  We have explored the chemistry of N-oxide heterocycles and imidazoles replacing ring D of the natural product (+)-calanolide A, and have synthesized 12 new analogues, two of which were active against both R Mtb and NR Mtb with MIC values of 12.5 mu g/mL, which would lead to further optimization for more potent anti-TB candidates. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.11.001

文献信息

• Scaffold-hopping strategy toward calanolides with nitrogen-containing heterocycles
  作者：Xiao-Yong Guo、Gang Liu

  DOI：10.1016/j.cclet.2013.03.007

  日期：2013.4

  (+)-Calanolide A was the first natural product identified as an active agent against HIV-1 and Mycobacterium tuberculosis (Mtb). In devising a scaffold-hopping strategy of structure modification of (+)-calanolide A, we focused on the synthesis of calanolides by replacing ring D with various five or six membered nitrogen-containing heterocycles, hoping to get further understanding of the structure-activity relationship. (C) 2013 Gang Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  （+)-Calanolide A是首个被确认为对HIV-1和结核杆菌（Mtb）有效的天然产物。在设计针对(+)-calanolide A的结构改进方案时，我们采用了“结构跳板”策略，专注于通过替代环D来合成各种新型的含氮杂环（五元或六元），这有助于进一步揭示其构效关系。 (C) 2013 Gang Liu. 本文由Elsevier B.V.代表中国化学会出版。保留所有权利。
• Synthetic Calanolides with Bactericidal Activity against Replicating and Nonreplicating <i>Mycobacterium tuberculosis</i>
  作者：Purong Zheng、Selin Somersan-Karakaya、Shichao Lu、Julia Roberts、Maneesh Pingle、Thulasi Warrier、David Little、Xiaoyong Guo、Steven J. Brickner、Carl F. Nathan、Ben Gold、Gang Liu

  DOI：10.1021/jm4019228

  日期：2014.5.8

  It is urgent to introduce new drugs for tuberculosis to shorten the prolonged course of treatment and control drug-resistant Mycobacterium tuberculosis (Mtb). One strategy toward this goal is to develop antibiotics that eradicate both replicating (R) and nonreplicating (NR) Mtb. Naturally occurring (+)-calanolide A was active against R-Mtb. The present report details the design, synthesis, antimycobacterial activities, and structure-activity relationships of synthetic calanolides. We identified potent dual-active nitro-containing calanolides with minimal in vitro toxicity that were cidal to axenic Mtb and Mtb in human macrophages, while sparing Gram-positive and -negative bacteria and yeast. Two of the nitrobenzofuran-containing lead compounds were found to be genotoxic to mammalian cells. Although genotoxicity precluded clinical progression, the profound, selective mycobactericidal activity of these calanolides will be useful in identifying pathways for killing both R- and NR-Mtb, as well as in further structure-based design of more effective and drug-like antimycobacterial agents.
• N-Oxide heterocycles and imidazoles replacing ring D of calanolides against Mycobacterium tuberculosis
  作者：Zi-Jie Liu、Xiao-Yong Guo、Gang Liu

  DOI：10.1016/j.cclet.2015.11.001

  日期：2016.1

  We have explored the chemistry of N-oxide heterocycles and imidazoles replacing ring D of the natural product (+)-calanolide A, and have synthesized 12 new analogues, two of which were active against both R Mtb and NR Mtb with MIC values of 12.5 mu g/mL, which would lead to further optimization for more potent anti-TB candidates. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.