(10alpha,11beta,12beta)-(-)-11,12-二氢-12-羟基-6,6,10,11-四甲基-4-苯基-2H,6H,10H-苯并(1,2-b:3,4-b':5,6-b'')三吡喃-2-酮 | 65025-62-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 中文名称: (10alpha,11beta,12beta)-(-)-11,12-二氢-12-羟基-6,6,10,11-四甲基-4-苯基-2H,6H,10H-苯并(1,2-b:3,4-b':5,6-b'')三吡喃-2-酮
• 英文名称: soulattrolide
• 英文别名: (16S,17R,18S)-18-hydroxy-10,10,16,17-tetramethyl-6-phenyl-3,9,15-trioxatetracyclo[12.4.0.02,7.08,13]octadeca-1(14),2(7),5,8(13),11-pentaen-4-one
• CAS: 65025-62-9
• 化学式: C₂₅H₂₄O₅
• 分子量: 404.463
• InChiKey: BXENDTPSKAICGV-RXSFTSLZSA-N

物化性质

• 熔点：
  177-181 °C
• 沸点：
  564.7±50.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)
• LogP：
  5.580 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (10alpha,11beta,12beta)-(-)-11,12-二氢-12-羟基-6,6,10,11-四甲基-4-苯基-2H,6H,10H-苯并(1,2-b:3,4-b':5,6-b'')三吡喃-2-酮 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、202.65 kPa 条件下， 反应 2.0h， 以57%的产率得到(10S,11R,12S)-12-Hydroxy-6,6,10,11-tetramethyl-4-phenyl-7,8,11,12-tetrahydro-6H,10H-dipyrano[2,3-f;2',3'-h]chromen-2-one
  参考文献：
  名称：

  Anti-HIV natural product (+)-calanolide A is active against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis

  摘要：

  Naturally occurring anti-HIV-1 agent (+)-calanolide A was found to be active against all of the strains of Mycobacterium tuberculosis tested, including those resistant to the standard antitubercular drugs. Efficacy evaluations in macrophages revealed that (+)-calanolide A significantly inhibited intracellular replication of M. tuberculosis H37Rv at concentrations below the MIC observed in vitro. Preliminary mechanistic studies indicated that (+)-calanolide A rapidly inhibits RNA and DNA synthesis followed by an inhibition of protein synthesis. Compared with known inhibitors, this scenario is more similar to effects observed with rifampin, an inhibitor of RNA synthesis. Since (+)-calanolide A was active against a rifampin-resistant strain, it is believed that these two agents may involve different targets. (+)-Calanolide A and its related pyranocoumarins are the first class of compounds identified to possess antimycobacterial and antiretroviral activities, representing a new pharmacophore for anti-TB activity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.11.012
• 作为产物：
  描述：

  、 、 甲基-4,6-二脱氧-2,3-O-异亚丙基-4-甲基吡喃糖苷 、 、 12-hydroxy-6,6,10,11-tetramethyl-4-propyl-11,12-dihydro-6H,10H-dipyrano[2,3-f;2',3'-h]chromen-2-one 在 二氧化铂 氢气 、 ethyl acetate n-hexane 作用下， 以 甲醇 为溶剂， 以to give 9.0 mg of 7,8-dihydrocalanolide A (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5)的产率得到(10alpha,11beta,12beta)-(-)-11,12-二氢-12-羟基-6,6,10,11-四甲基-4-苯基-2H,6H,10H-苯并(1,2-b:3,4-b':5,6-b'')三吡喃-2-酮
  参考文献：
  名称：

  Calanolide and related antiretroviral compounds, compositions, and uses

  摘要：

  本发明提供了一种新型抗病毒化合物，称为卡拉诺酮和相关化合物及其衍生物，可以从Calophyllum属植物中分离出来或从该属植物的化合物中衍生出来，符合本发明方法。这些化合物及其衍生物可以单独使用或与其他抗病毒药物组合使用在组成物中，例如制药组成物中，以抑制病毒的生长或复制，例如逆转录病毒，特别是人类免疫缺陷病毒，具体地是HIV-1或HIV-2。

  公开号：

  US05591770A1

文献信息

• Calanolide and related antiviral compounds, compositions, and uses thereof
  申请人：——

  公开号：US20020086898A1

  公开（公告）日：2002-07-04

  The present invention provides novel antiviral compounds, refered to as calanolides, related compounds, and their derivatives, which may be isolated from plants, or derived from compounds from plants, of the genus Calophyllum in accordance with the present inventive method. The compounds and their derivatives may be used alone or in combination with other antiviral agents in compositions, such as pharmaceutical compositions, to inhibit the growth or replication of a virus, such as a retrovirus, in particular a human immunodeficiency virus, specifically HIV-1 or HIV-2.

  本发明提供了新型的抗病毒化合物，称为卡拉诺利德（calanolides）、相关化合物及其衍生物，可从山竹子属（Calophyllum）植物中分离或从该属植物的化合物中衍生出来，符合本发明方法。这些化合物及其衍生物可单独使用或与其他抗病毒药物组合在一起，形成组成物，如制药组成物，以抑制病毒的生长或复制，如逆转录病毒，特别是人类免疫缺陷病毒，具体是HIV-1或HIV-2。
• Calanolide and related antiviral compounds, compositions, and uses
  申请人：The United States of America as represented by the Department of Health

  公开号：US05859049A1

  公开（公告）日：1999-01-12

  The present invention provides novel antiviral compounds, refered to as calanolides, related compounds, and their derivatives, which may be isolated from plants, or derived from compounds from plants, of the genus Calophyllum in accordance with the present inventive method. The compounds and their derivatives may be used alone or in combination with other antiviral agents in compositions, such as pharmaceutical compositions, to inhibit the growth or replication of a virus, such as a retrovirus, in particular a human immunodeficiency virus, specifically HIV-1 or HIV-2.

  本发明提供了一种新的抗病毒化合物，称为卡洛利德（calanolides），相关化合物及其衍生物。这些化合物可以从喜树属（Calophyllum）植物中分离出来，或者从这些植物中的化合物衍生而来，根据本发明的方法。这些化合物及其衍生物可以单独使用或与其他抗病毒药物组合在一起，制成药物组合物，以抑制病毒的生长或复制，例如逆转录病毒，特别是人类免疫缺陷病毒，具体包括HIV-1或HIV-2。
• Absolute Stereochemistry of Soulattrolide and Its Analogues
  作者：Xiongwei Shi、Athula B. Attygalle、Adam Liwo、Ming-Hong Hao、Jerrold Meinwald、H. Ranjith W. Dharmaratne、W. M. Anoja P. Wanigasekera

  DOI：10.1021/jo9717752

  日期：1998.2.1

  The absolute stereochemistry of a group of dipyranocoumarins, some of which are potent inhibitors of HIV-1 reverse transcriptase, was examined. Soulattrolide 2H,6H,10N-benzo[1,2-b:3,4-b':5,6-b]tripyran-2-one, 11,12-dihydro-12-hydroxy-6,6,10,11-tetra [10S-(10 alpha,11 beta,12 beta)]-; CAS Registry No. 65025-62-9} and cordatolide B, two of these dipyranocoumarins, were converted to alpha-methoxy-alpha-(trifluoromethyl)phenylacetate (MTPA) derivatives and investigated by H-1 NMR spectroscopy. A correlation of H-1 NMR chemical shift differences with those predicted by Mosher's concept alone was inadequate to assign confidently the absolute stereochemistries, due to the fact that in both of these molecules too few protons are present on one side of the MTPA plane. However, energetically favored conformations obtained by molecular mechanics calculations provided satisfactory rationalizations for the observed anisotropic shifts in H-1 NMR data. The combined results of the two techniques allow us to assign the absolute configuration of both soulattrolide and cordatolide B as (10S,11R,12S). The absolute configurations of the other structurally related inhibitors, including inophyllums B, D, and P, costatolide, calanolides A, B, and C, and cordatolide A, are also assigned on the basis of chemical conversions and correlations of their chiroptical properties. Subtleties in the application of the Cahn-Ingold-Prelog rules to the designation of R or S configurations at some positions in these compounds make basically trivial errors particularly easy.
• Calanolide and related antiretroviral compounds, compositions, and uses
  申请人：The United States of America as represented by the Department of Health

  公开号：US05591770A1

  公开（公告）日：1997-01-07

  The present invention provides novel antiviral compounds, refered to as calanolides, related compounds, and their derivatives, which may be isolated from plants, or derived from compounds from plants, of the genus Calophyllum in accordance with the present inventive method. The compounds and their derivatives may be used alone or in combination with other antiviral agents in compositions, such as pharmaceutical compositions, to inhibit the growth or replication of a virus, such as a retrovirus, in particular a human immunodeficiency virus, specifically HIV-1 or HIV-2.

  本发明提供了一种新型抗病毒化合物，称为卡拉诺酮和相关化合物及其衍生物，可以从Calophyllum属植物中分离出来或从该属植物的化合物中衍生出来，符合本发明方法。这些化合物及其衍生物可以单独使用或与其他抗病毒药物组合使用在组成物中，例如制药组成物中，以抑制病毒的生长或复制，例如逆转录病毒，特别是人类免疫缺陷病毒，具体地是HIV-1或HIV-2。
• Anti-HIV natural product (+)-calanolide A is active against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis
  作者：Ze-Qi Xu、William W Barrow、William J Suling、Louise Westbrook、Esther Barrow、Yuh-Meei Lin、Michael T Flavin

  DOI：10.1016/j.bmc.2003.11.012

  日期：2004.3

  Naturally occurring anti-HIV-1 agent (+)-calanolide A was found to be active against all of the strains of Mycobacterium tuberculosis tested, including those resistant to the standard antitubercular drugs. Efficacy evaluations in macrophages revealed that (+)-calanolide A significantly inhibited intracellular replication of M. tuberculosis H37Rv at concentrations below the MIC observed in vitro. Preliminary mechanistic studies indicated that (+)-calanolide A rapidly inhibits RNA and DNA synthesis followed by an inhibition of protein synthesis. Compared with known inhibitors, this scenario is more similar to effects observed with rifampin, an inhibitor of RNA synthesis. Since (+)-calanolide A was active against a rifampin-resistant strain, it is believed that these two agents may involve different targets. (+)-Calanolide A and its related pyranocoumarins are the first class of compounds identified to possess antimycobacterial and antiretroviral activities, representing a new pharmacophore for anti-TB activity. (C) 2003 Elsevier Ltd. All rights reserved.