(-)-cyclomorusin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (-)-cyclomorusin
• 英文别名: (15S)-11,19-dihydroxy-7,7-dimethyl-15-(2-methylprop-1-enyl)-2,8,16-trioxapentacyclo[12.8.0.03,12.04,9.017,22]docosa-1(14),3(12),4(9),5,10,17(22),18,20-octaen-13-one
• 化学式: C₂₅H₂₂O₆
• 分子量: 418.446
• InChiKey: GDQXJMLXEYSICD-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-cyclomorusin 在 palladium 10% on activated carbon 、 氢气 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 (-)-dehydrocyclomorusin
  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
• 作为产物：
  描述：

  环桑色烯 在 Daicel CHIRALPAK AD-H 作用下， 以 正己烷 、 异丙醇 为溶剂， 以0.2 mg的产率得到(+)-cyclomorusin
  参考文献：
  名称：

  来自桑树根皮的具有 α-葡萄糖苷酶抑制活性的异戊二烯化黄烷酮对映异构体

  摘要：

  对一种名为 Sang-Bai-Pi（桑树根皮）的著名中药的极性馏分进行集中化学研究，产生了一组异戊二烯化黄烷酮。根据 HRMS、NMR 和 ECD 分析，新化合物被鉴定为具有相同构成结构的四对映异构体 （1a/1b–4a/4b）。还通过手性柱上的 HPLC 分析和分离了几种先前报道的已知外消旋共代谢物，并首次通过 ECD 技术建立了纯对映异构体的绝对构型。进一步测试了这些分离株对抗糖尿病靶标 α-糖苷酶的抑制作用，与阳性对照阿卡波糖相比，它们中的大多数显示出不错的抑制活性。通过动力学实验探索了两种选定化合物（3a和4b）的相互作用机制，揭示了对酶的混合抑制模式。

  DOI：

  10.1002/cbdv.202401646

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.