6,12-Dihydroxy-9-(1-hydroxy-isopropyl)-3,3-dimethyl-1,2,3-trihydro-8H,9H-benzo[f]pyrano[2',3'-8,7]chromeno[3,2-d]oxepin-7-one | 67690-77-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6,12-Dihydroxy-9-(1-hydroxy-isopropyl)-3,3-dimethyl-1,2,3-trihydro-8H,9H-benzo[f]pyrano[2',3'-8,7]chromeno[3,2-d]oxepin-7-one
• 英文别名: 11,20-dihydroxy-16-(2-hydroxypropan-2-yl)-7,7-dimethyl-2,8,17-trioxapentacyclo[12.9.0.03,12.04,9.018,23]tricosa-1(14),3(12),4(9),10,18(23),19,21-heptaen-13-one
• CAS: 67690-77-1
• 化学式: C₂₅H₂₆O₇
• 分子量: 438.477
• InChiKey: HOSUXHGFPNMDFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  morusin 在 manganese(IV) oxide 作用下， 以 甲苯 为溶剂， 反应 72.0h， 以9 mg的产率得到6,12-Dihydroxy-9-(1-hydroxy-isopropyl)-3,3-dimethyl-1,2,3-trihydro-8H,9H-benzo[f]pyrano[2',3'-8,7]chromeno[3,2-d]oxepin-7-one
  参考文献：
  名称：

  Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba : Isolation, modification, and structure-activity relationship study

  摘要：

  The bioassay-guided phytochemical study of a traditional Chinese medicine Moms alba led to the isolation of 18 prenylated flavonoids (1-18), of which (+/-)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by, methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC50 values ranging from 0.0054 to 0.40 mu M, being more active than the positive control rolipram (IC50 = 0.62 mu M). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.057

文献信息

• Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba : Isolation, modification, and structure-activity relationship study
  作者：Yan-Qiong Guo、Gui-Hua Tang、Lan-Lan Lou、Wei Li、Bei Zhang、Bo Liu、Sheng Yin

  DOI：10.1016/j.ejmech.2017.12.057

  日期：2018.1

  The bioassay-guided phytochemical study of a traditional Chinese medicine Moms alba led to the isolation of 18 prenylated flavonoids (1-18), of which (+/-)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by, methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC50 values ranging from 0.0054 to 0.40 mu M, being more active than the positive control rolipram (IC50 = 0.62 mu M). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling. (C) 2017 Elsevier Masson SAS. All rights reserved.