3-(Hydroxymethyl)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-2-naphthoic acid lactone | 26560-83-8

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基萘木脂素
• 英文名称: 3-(Hydroxymethyl)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-2-naphthoic acid lactone
• 英文别名: 6,7-dimethoxy-9-(3,4,5-trimethoxy-phenyl)-3H-naphtho[2,3-c]furan-1-one；Trimethylplicatinaphthalin, 2-(Hydroxymethyl)-6,7-dimethoxy-4-(3',4',5'-trimethoxy-phenyl)-3-naphthalincarbonsaeurelacton；Trimethylplicatinaphthalin；6,7-Dimethoxy-9-(3,4,5-trimethoxy-phenyl)-3H-naphtho[2,3-c]furan-1-one；6,7-dimethoxy-4-(3,4,5-trimethoxyphenyl)-1H-benzo[f][2]benzofuran-3-one
• CAS: 26560-83-8
• 化学式: C₂₃H₂₂O₇
• 分子量: 410.423
• InChiKey: VFULRIWYLLHLAZ-UHFFFAOYSA-N

物化性质

• 熔点：
  233-235 °C
• 沸点：
  593.6±50.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(Hydroxymethyl)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-2-naphthoic acid lactone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以79%的产率得到2,3-bis(hydroxymethyl)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)naphthalene
  参考文献：
  名称：

  新型选择性PDE IV抑制剂作为抗哮喘药。一系列1-芳基-2,3-双（羟甲基）萘木脂素的合成及生物活性。

  摘要：

  已经合成了一系列的1-芳基-2,3-双（羟甲基）萘木酚素，并对其选择性抑制豚鼠分离的PDE IV的能力进行了评估。1-吡啶环被吡啶酮环取代导致其对PDE IV的选择性比PDE III显着提高。最有效和最具选择性的化合物涉及在C-1处带有N-烷基吡啶酮环的化合物。这些化合物还显示出有效的抗痉挛活性，而不会引起豚鼠心率的显着变化。最有效的化合物是6,7-二乙氧基-2，3-双（羟甲基）-1- [1-（2-甲氧基乙基）-2-氧代-吡啶-4-基] nap hth alene（17f），ED50值在豚鼠中，组胺诱导的和抗原诱导的支气管收缩分别为0.08和2.3 mg / kg iv。

  DOI：

  10.1021/jm9509096
• 作为产物：
  描述：

  6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene-3-carboxylic acid 在 sodium tetrahydroborate 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.17h， 生成 3-(Hydroxymethyl)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-2-naphthoic acid lactone
  参考文献：
  名称：

  1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor

  摘要：

  1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 > 16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3,4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-carboxylate (35) (27q, EC50 = 0.10 mu M; 35, EC50 = 0.20 mu M) and was selected for further biological evaluation.

  DOI：

  10.1021/jm9807048

文献信息

• A rapid entry into podophyllotoxin congeners: Synthesis of justicidin B
  作者：Ahmed Kamal、Mohsen Daneshtalab、Ronald G. Micetich

  DOI：10.1016/s0040-4039(00)76691-3

  日期：1994.6

  A facile synthesis of justicidin B is described, as well as related podophyllum lignans by employing Michael Initiated Ring Closure strategy followed by desulfurization mediated by nickel-containing complex reducing agent.

  描述了通过使用迈克尔引发的闭环策略，然后由含镍的复合还原剂介导的脱硫，轻松合成了justicidin B以及相关的鬼臼木。
• A new two-step synthesis of 1-arylnaphthalene lignans from cyanohydrins
  作者：Tsuyoshi Ogiku、Masahiko Seki、Masami Takahashi、Hiroshi Ohmizu、Tameo Iwasaki

  DOI：10.1016/s0040-4039(00)97879-1

  日期：1990.1

  1-Arylnaphthalene lignans were synthesized in good yields from O-t-butyldimethylsilylcyanohydrins in two steps based on a new approach involving a tandem conjugate addition-aldol reaction, followed by an acid-catalyzed construction of the naphthalene ring.

  基于涉及串联共轭加成-醛醇缩合反应的新方法，然后通过酸催化的萘环的构建，由O-叔丁基二甲基甲硅烷基氰醇分两步以高收率合成了1-芳基萘木酚素。
• Efficient Syntheses of 1-Arylnaphthalene Lignan Lactones and Related Compounds from Cyanohydrins
  作者：Tsuyoshi Ogiku、Sin-ich Yoshida、Hiroshi Ohmizu、Tameo Iwasaki

  DOI：10.1021/jo00119a041

  日期：1995.7

  1-Arylnaphthalene lignan lactones were synthesized in good yields from O-(tert-butyldimethylsilyl)cyanohydrins in two steps based on a conjugate addition-aldol reaction, followed by acid-catalyzed closure to form the naphthalene ring. 4-Hydroxy-1-arylnaphthalene lignan lactones were also synthesized by conjugate addition-aldol reaction, followed by aromatization-lactonization.
• OGIKU, TSUYOSHI;SEKI, MASAHIKO;TAKAHASHI, MASAMI;OHMIZU, HIROSHI;IWASAKI,+, TETRAHEDRON LETT., 31,(1990) N8, C. 5487-5490
  作者：OGIKU, TSUYOSHI、SEKI, MASAHIKO、TAKAHASHI, MASAMI、OHMIZU, HIROSHI、IWASAKI,+

  DOI：——

  日期：——
• 1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor
  作者：Tatsuzo Ukita、Yoshinori Nakamura、Akira Kubo、Yasuo Yamamoto、Masami Takahashi、Jun Kotera、Tomohiro Ikeo

  DOI：10.1021/jm9807048

  日期：1999.4.1

  1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 > 16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3,4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-carboxylate (35) (27q, EC50 = 0.10 mu M; 35, EC50 = 0.20 mu M) and was selected for further biological evaluation.