红松内酯 | 31685-80-0

• 物质功能分类: 天然产物 - 萜类
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 红松内酯
• 英文名称: Pinusolide
• 英文别名: methyl 1,4a-dimethyl-6-methylidene-5-[2-(2-oxo-2,5-dihydrofuran-3-yl)ethyl]decahydronaphthalene-1-carboxylate；methyl (1S,4aR,5S,8aR)-1,4a-dimethyl-6-methylidene-5-[2-(5-oxo-2H-furan-4-yl)ethyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylate
• CAS: 31685-80-0
• 化学式: C₂₁H₃₀O₄
• 分子量: 346.467
• InChiKey: WTKBZJAWPZXKJU-NLEAXPPASA-N

物化性质

• 熔点：
  82-84 °C(Solv: ligroine (8032-32-4))
• 沸点：
  465.3±38.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  4.520 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  红松内酯 在 Celite 、 sodium aluminum diethyl dihydride 、 silver carbonate 作用下， 以 乙醚 、 苯 为溶剂， 反应 3.0h， 生成 medigenin
  参考文献：
  名称：

  In Vitro Platelet-Activating Factor Receptor Binding Inhibitory Activity of Pinusolide Derivatives: A Structure−Activity Study

  摘要：

  Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was found to be a potent platelet-activating factor (PAF) receptor binding antagonist. To investigate the structure-activity relationship and find derivatives with improved pharmacological profiles, 17 pinusolide derivatives were prepared and tested for their ability to inhibit the PAF receptor binding. The results demonstrated that the carboxymethyl ester group at C-19, the integrity of the alpha,beta-unsaturated butenolide ring, and the exocyclic olefinic function of pinusolide are all necessary for its maximum PAF receptor binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8 was found to be as potent as pinusolide. The results also suggested that several derivatives warrant further pharmaceutical and pharmacological studies due to their improved water solubility (8 and 11) and apparent lack of susceptibility to Michael-type nucleophilic addition (13 and 18).

  DOI：

  10.1021/jm970569j
• 作为产物：
  描述：

  methyl 5-[2-(2,5-dimethoxy-2,5-dihydrofuran-3-yl)ethyl]-1,4a-dimethyl-6-methylidene-decahydronaphthalene-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以67%的产率得到红松内酯
  参考文献：
  名称：

  Synthetic transformations of higher terpenoids: XIV. Synthesis of pyrrololabdanoids from lambertianic acid

  摘要：

  Treatment of lambertianic acid methyl ester with lead tetraacetate gave terpenoid 2,5-diacetoxydihydrofuran which reacted with primary amines to yield 3 -terpenyl -substituted pyrrol-2(5H)-ones; the reaction with bydrazine led to the corresponding pyridazine derivative. The obtained furanoterpenoids underwent oxidative methoxylation by the action of N-chlorobenzenesulfonamide or N-bromosuccinimide in methanol. 2,5-Dimethoxydihydrofurans thus formed were smoothly converted into 3-substituted furan-2(5H)-one in acid medium. Hydrogenation of 2,5-dimethoxydihydrofurans, followed by treatment with amines, gave 1,3-disubstituted pyrroles.

  DOI：

  10.1134/s1070428006060030

文献信息

• Gram-scale synthesis of pinusolide and evaluation of its antileukemic potential
  作者：E.E. Shults、J. Velder、H.-G. Schmalz、S.V. Chernov、T.V. Rubalova、Y.V. Gatilov、G. Henze、G.A. Tolstikov、A. Prokop

  DOI：10.1016/j.bmcl.2006.05.077

  日期：2006.8

  Pinusolide (1), a known platelet-activating factor (PAF) receptor binding antagonist, was synthesized from lambertianic acid (2), a labdane-type diterpene readily accessible in multigram quantities from the Siberian pine tree. It was shown that 1 not only decreases the proliferation activity of tumor cells at relatively low concentrations but specifically induces apoptosis at 100 PM via the mitochondrial pathway in the Burkitt lymphoma cell line BJAB. Also, using primary lymphoblasts and leukemic cells from children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), a significant DNA fragmentation in pinusolide-treated cells could be detected in an ex vivo apoptosis assay. (c) 2006 Elsevier Ltd. All rights reserved.
• Pinusolide, a new diterpenoid from Pinus sibirica and P. korsensis
  作者：V. A. Raldugin、A. I. Lisina、N. K. Kashtanova、V. A. Pentegova

  DOI：10.1007/bf00563440

  日期：1970.9
• GRISHKO, V. V.;SHEVTSOV, S. A.;DEMENKOVA, L. I.;RALDUGIN, V. A.;LYANDRES,+, SIB. XIM. ZH.,(1991) N, S. 94-97
  作者：GRISHKO, V. V.、SHEVTSOV, S. A.、DEMENKOVA, L. I.、RALDUGIN, V. A.、LYANDRES,+

  DOI：——

  日期：——
• Synthetic transformations of higher terpenoids: XIV. Synthesis of pyrrololabdanoids from lambertianic acid
  作者：S. V. Chernov、E. E. Shul’ts、M. M. Shakirov、G. A. Tolstikov

  DOI：10.1134/s1070428006060030

  日期：2006.6

  Treatment of lambertianic acid methyl ester with lead tetraacetate gave terpenoid 2,5-diacetoxydihydrofuran which reacted with primary amines to yield 3 -terpenyl -substituted pyrrol-2(5H)-ones; the reaction with bydrazine led to the corresponding pyridazine derivative. The obtained furanoterpenoids underwent oxidative methoxylation by the action of N-chlorobenzenesulfonamide or N-bromosuccinimide in methanol. 2,5-Dimethoxydihydrofurans thus formed were smoothly converted into 3-substituted furan-2(5H)-one in acid medium. Hydrogenation of 2,5-dimethoxydihydrofurans, followed by treatment with amines, gave 1,3-disubstituted pyrroles.
• In Vitro Platelet-Activating Factor Receptor Binding Inhibitory Activity of Pinusolide Derivatives: A Structure−Activity Study
  作者：Byung Hoon Han、Hyun Ok Yang、Young-Hwa Kang、Dae-Yeon Suh、Hyun Jung Go、Wan-Jin Song、Yong Chul Kim、Man Ki Park

  DOI：10.1021/jm970569j

  日期：1998.7.1

  Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was found to be a potent platelet-activating factor (PAF) receptor binding antagonist. To investigate the structure-activity relationship and find derivatives with improved pharmacological profiles, 17 pinusolide derivatives were prepared and tested for their ability to inhibit the PAF receptor binding. The results demonstrated that the carboxymethyl ester group at C-19, the integrity of the alpha,beta-unsaturated butenolide ring, and the exocyclic olefinic function of pinusolide are all necessary for its maximum PAF receptor binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8 was found to be as potent as pinusolide. The results also suggested that several derivatives warrant further pharmaceutical and pharmacological studies due to their improved water solubility (8 and 11) and apparent lack of susceptibility to Michael-type nucleophilic addition (13 and 18).