5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | 34107-31-8

• 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: 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one
• 英文别名: 2,2-dimethyl-5-hydroxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-8-on；5-Hydroxy-2,2-dimethyl-10-propyl-pyrano[2,3-h]chromen-8-one；5-hydroxy-2,2-dimethyl-10-propylpyrano[2,3-f]chromen-8-one
• CAS: 34107-31-8
• 化学式: C₁₇H₁₈O₄
• 分子量: 286.328
• InChiKey: PTXVUDJOJQSVCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.5h， 生成 2,2-dimethyl-10-propyl-5-(p-tolylethynyl)-2H,8H-pyrano[2,3-f]chromen-8-one
  参考文献：
  名称：

  Synthetic Calanolides with Bactericidal Activity against Replicating and Nonreplicating Mycobacterium tuberculosis

  摘要：

  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.

  DOI：

  10.1021/jm4019228
• 作为产物：
  描述：

  2,2-Dimethyl-5-propionyloxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-8-one 在 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 7.0h， 以52%的产率得到5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one
  参考文献：
  名称：

  Methods for preparing antiviral calanolide compounds

  摘要：

  本发明涉及制备2,2-二甲基-5-酰氧基-10-丙基-2H,8H-苯并[1,2-b:3,4-b']二吡喃-8-酮（5）和2,2-二甲基-5-羟基-10-丙基-2H,8H-苯并[1,2-b:3,4-b']二吡喃-8-酮（6）的方法，以及它们作为合成抗病毒卡那里类化合物的中间体的用途。例如，对化合物5进行Fries重排或对6进行Friedel-Crafts反应，产生中间体2,2-二甲基-5-羟基-6-丙酰基-10-丙基-2H,8H-苯并[1,2-b:3,4-b']二吡喃-8-酮（4），然后可以将其转化为（+）-卡那里A和（-）-卡那里B。化合物6与适当手性分子在Mitsunobu反应或亲核取代下的偶联导致抗病毒卡那里类化合物的不对称合成。

  公开号：

  US06369241B1

文献信息

• Chemical Library and Structure–Activity Relationships of 11-Demethyl-12-oxo Calanolide A Analogues as Anti-HIV-1 Agents
  作者：Tao Ma、Li Liu、Hai Xue、Li Li、Chunyan Han、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm701405p

  日期：2008.3.13

  (+)-Calanolide A (1) as a natural product was previously found as an inhibitor of HIV-1 reverse tratiscriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A (15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC(50) = 0.11 mu M, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC(50) = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.

  (+)-Calanolide A (1) 作为一种天然产物，先前被发现是HIV-1逆转录酶的抑制剂。在我们对其模板的进一步研究中，外消旋的11-去甲基-12-酮基calanolide A (15) 被发现。与(+)-calanolide A相比，它在C-11和C-12位上少两个手性碳中心，但其对HIV-1的抑制活性相当，并且具有更好的治疗指数（EC(50) = 0.11 μM，TI = 818）。随后，基于其结构核心设计并合成了一个化合物库，并在本文中引入了九个多样性点。体外评估抗HIV-1活性得出了它们的结构-活性关系（SARs）。发现了一个新的化合物（10-溴甲基-11-去甲基-12-酮基calanolide A，123），其对HIV-1的抑制效力和治疗指数（EC(50) = 2.85 nM，TI > 10,526）显著高于该类化合物。这一发现提供了非常重要的线索，即对C环的C-10位进行修饰，可能会得到对HIV-1活性更好的药物候选物。
• 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。
• 1-Nicotinoylbenzotriazole: A Convenient Tool for Site-Selective Protection of 5,7-Dihydroxycoumarins
  作者：Ramil F. Fatykhov、Igor A. Khalymbadzha、Oleg N. Chupakhin、Valery N. Charushin、Anna K. Inyutina、Pavel A. Slepukhin、Victor G. Kartsev

  DOI：10.1055/s-0039-1690104

  日期：2019.10

  intermediate for the synthesis of calanolide A, an HIV reverse transcriptase and Mycobacterium tuberculosis inhibitor, and its active analogues. 1-Nicotinoylbenzotriazole (NicBt) was uncovered as an efficient protecting agent for the site-selective acylation of resorcinol-type phenolic groups with almost equal reactivity. The use of NicBt allows selective protection of the 7-OH group in 5,7-dihydroxycoumarins

  抽象的 1-烟酰苯并三唑（NicBt）被发现为间苯二酚型酚基团具有几乎相同反应活性的位点选择性酰化的有效保护剂。使用NicBt可以在一个简单的可扩展步骤中选择性保护5,7-二羟基香豆素中的7-OH基团，而将烟酰化与甲苯磺酸化-烯基锡酰化或甲硅烷基化-花生素化基团结合可得到5-OH保护的5,7-二羟基香豆素。此外，烟酰化的5,7-二羟基香豆素被证明可用于克规模的三步法制备2,2-二甲基吡喃并[2,3- f ]香豆素，它是合成卡拉诺德A，HIV逆转录酶和结核分枝杆菌抑制剂及其活性类似物。 1-烟酰苯并三唑（NicBt）被发现为间苯二酚型酚基团具有几乎相同反应活性的位点选择性酰化的有效保护剂。使用NicBt可以在一个简单的可扩展步骤中选择性保护5,7-二羟基香豆素中的7-OH基团，而将烟酰化与甲苯磺酸化-烯基锡酰化或甲硅烷基化-花生素化基团结合可得到5-OH保护的5,7-二羟基香豆素。此外，烟酰化的5
• Process for the preparation of calanolide precursors
  申请人：Chirotech Technology, Inc.

  公开号：US06313320B1

  公开（公告）日：2001-11-06

  The present invention concerns compounds of the formula wherein R1, R2, R3, R4 and R6 each represent H or an organic group of up to 20 C atoms, or any pair of R2 and R3 or R2 and R6 or R4 and R6 forms a cyclic group, and R5SO2 is a cleavable protecting group in which R5 is an organic group of up to 20 C atoms. These compounds are useful as intermediates in the synthesis of calanolide A and related antiviral compounds.

  本发明涉及以下式的化合物，其中R1，R2，R3，R4和R6分别代表H或最多20个C原子的有机基团，或者任何一对R2和R3或R2和R6或R4和R6形成一个环状基团，而R5SO2是一个可断裂的保护基团，其中R5是最多20个C原子的有机基团。这些化合物可用作卡拉诺利德A及相关抗病毒化合物的合成中间体。
• Novel coumarin and chromene compounds and methods of preparation and use thereof for treating or preventing viral infections
  申请人：——

  公开号：US20030176494A1

  公开（公告）日：2003-09-18

  The present invention relates to methods of preparation and use of coumarin and chromene compounds for treating or preventing viral infections.

  本发明涉及制备和使用香豆素和色酮化合物治疗或预防病毒感染的方法。